1932
0
  1. Home
  2. A-Z Publications
  3. Annual Review of Immunology
  4. Volume 38, 2020
  5. Article

Annual Review of Immunology

Volume 38, 2020

Obsessive-Compulsive Behavior Isn't Necessarily a Bad Thing

Abstract

It is difficult to believe that in about 1960 practically nothing was known about the thymus and some of its products, T cells bearing αβ receptors for antigen. Thus I was lucky to join the field of T cell biology almost at its beginning, when knowledge about the cells was just getting off the ground and there was so much to discover. This article describes findings about these cells made by others and myself that led us all from ignorance, via complete confusion, to our current state of knowledge. I believe I was fortunate to practice science in very supportive institutions and with very collaborative colleagues in two countries that both encourage independent research by independent scientists, while simultaneously ignoring or somehow being able to avoid some of the difficulties of being a woman in what was, at the time, a male-dominated profession.

Keyword(s): autobiography, clonal deletion, major histocompatibility complex, positive selection, superantigens, T cell receptor, thymus
Loading

Article metrics loading...

/content/journals/10.1146/annurev-immunol-072319-033325
2020-04-26
2024-04-19
Loading full text...

Full text loading...

/deliver/fulltext/immunol/38/1/annurev-immunol-072319-033325.html?itemId=/content/journals/10.1146/annurev-immunol-072319-033325&mimeType=html&fmt=ahah

Literature Cited

  1. 1. 
    Marrack JR. 1934. Derived antigens as a means of studying the relation of specific combination to chemical structure. Proc. R. Soc. Med. 27:1063–65
     [Google Scholar]
  2. 2. 
    Mishell RI, Dutton RW. 1967. Immunization of dissociated spleen cell cultures from normal mice. J. Exp. Med. 126:423–42
     [Google Scholar]
  3. 3. 
    Claman HN. 1966. Human thymus cell cultures—evidence for two functional populations. Proc. Soc. Exp. Biol. Med. 121:236–40
     [Google Scholar]
  4. 4. 
    Claman HN, Chaperon EA, Triplett RF 1966. Thymus-marrow cell combinations: synergism in antibody production. Proc. Soc. Exp. Biol. Med. 122:1167–71
     [Google Scholar]
  5. 5. 
    Good RA, Dalmasso AP, Martinez C, Archer OK, Pierce JC, Papermaster BW 1962. The role of the thymus in development of immunologic capacity in rabbits and mice. J. Exp. Med. 116:773–96
     [Google Scholar]
  6. 6. 
    Good RA, Gabrielsen AE. 1964. The function of the thymus. Med. Sci. 15:54–61
     [Google Scholar]
  7. 7. 
    Miller JF. 1961. Immunological function of the thymus. Lancet 2:748–49
     [Google Scholar]
  8. 8. 
    Mitchison NA. 1971. The carrier effect in the secondary response to hapten-protein conjugates. I. Measurement of the effect with transferred cells and objections to the local environment hypothesis. Eur. J. Immunol. 1:10–17
     [Google Scholar]
  9. 9. 
    Rajewsky K, Schirrmacher V, Nase S, Jerne NK 1969. The requirement of more than one antigenic determinant for immunogenicity. J. Exp. Med. 129:1131–43
     [Google Scholar]
  10. 10. 
    Raff M. 1969. Theta isoantigen as a marker of thymus-derived lymphocytes in mice. Nature 224:378–79
     [Google Scholar]
  11. 11. 
    Raff MC, Wortis HH. 1970. Thymus dependence of theta-bearing cells in the peripheral lymphoid tissues of mice. Immunology 18:931–42
     [Google Scholar]
  12. 12. 
    Sell S, Gell PG. 1965. Studies on rabbit lymphocytes in vitro. I. Stimulation of blast transformation with an antiallotype serum. J. Exp. Med. 122:423–40
     [Google Scholar]
  13. 13. 
    Cooper MD, Raymond DA, Peterson RD, South MA, Good RA 1966. The functions of the thymus system and the bursa system in the chicken. J. Exp. Med. 123:75–102
     [Google Scholar]
  14. 14. 
    Munro A, Hunter P. 1970. In vitro reconstitution of the immune response of thymus-deprived mice to sheep red blood cells. Nature 225:277–78
     [Google Scholar]
  15. 15. 
    Dwyer JM, Mason S, Warner NL, Mackay IR 1971. Antigen binding lymphocytes in congenitally athymic (nude) mice. Nat. New Biol. 234:252–53
     [Google Scholar]
  16. 16. 
    Forget A, Potworowski EF, Richer G, Borduas AG 1970. Antigenic specificities of bursal and thymic lymphocytes in the chicken. Immunology 19:465–68
     [Google Scholar]
  17. 17. 
    Unanue ER. 1971. Antigen-binding cells. I. Their identification and role in the immune response. J. Immunol. 107:1168–74
     [Google Scholar]
  18. 18. 
    Bach JF. 1971. Antigen recognition by T-cells and its suppression. Significance and origin of rosette-forming cells. Ann. Rheum. Dis. 30:565–73
     [Google Scholar]
  19. 19. 
    Greaves MF, Moller E, Moller G 1970. Studies on antigen-binding cells. II. Relationship to antigen-sensitive cells. Cell Immunol 1:386–403
     [Google Scholar]
  20. 20. 
    Hunter P, Munro A, McConnell I 1972. Properties of educated T cells for rosette formation and cooperation with B cells. Nat. New Biol. 236:52–53
     [Google Scholar]
  21. 21. 
    Hunter P, Munro AJ. 1970. The induction of an immune response in vitro to a protein antigen (rabbit Fab′2). Immunology 19:491–99
     [Google Scholar]
  22. 22. 
    Gorczynski RM, Miller RG, Phillips RA 1972. Initiation of antibody production to sheep erythrocytes in vitro: replacement of the requirement for T-cells with a cell-free factor isolated from cultures of lymphoid cells. J. Immunol. 108:547–51
     [Google Scholar]
  23. 23. 
    Schimpl A, Wecker E. 1972. Replacement of T-cell function by a T-cell product. Nat. New Biol. 237:15–17
     [Google Scholar]
  24. 24. 
    Hunter P, Kettman JR. 1974. Mode of action of a supernatant activity from T-cell cultures that nonspecifically stimulates the humoral immune response. PNAS 71:512–16
     [Google Scholar]
  25. 25. 
    Cantor H. 1972. T cells and the immune response. Prog. Biophys. Mol. Biol. 25:73–82
     [Google Scholar]
  26. 26. 
    Hunter PM, Kappler JW, Kettman JR 1974. The frequency and activity of single helper T cells. J. Immunol. 113:830–34
     [Google Scholar]
  27. 27. 
    Lederman S, Yellin MJ, Inghirami G, Lee JJ, Knowles DM, Chess L 1992. Molecular interactions mediating T-B lymphocyte collaboration in human lymphoid follicles: roles of T cell-B-cell-activating molecule (5c8 antigen) and CD40 in contact-dependent help. J. Immunol. 149:3817–26
     [Google Scholar]
  28. 28. 
    Noelle RJ, Roy M, Shepherd DM, Stamenkovic I, Ledbetter JA, Aruffo A 1992. A 39-kDa protein on activated helper T cells binds CD40 and transduces the signal for cognate activation of B cells. PNAS 89:6550–54
     [Google Scholar]
  29. 29. 
    Klein G. 1992. Physiology or Medicine 1980. Scand. J. Immunol. 35:374–75
     [Google Scholar]
  30. 30. 
    Katz DH, Graves M, Dorf ME, Dimuzio H, Benacerraf B 1975. Cell interactions between histoincompatible T and B lymphocytes. VII. Cooperative responses between lymphocytes are controlled by genes in the I region of the H-2 complex. J. Exp. Med. 141:263–68
     [Google Scholar]
  31. 31. 
    Katz DH, Hamaoka T, Dorf ME, Benacerraf B 1973. Cell interactions between histoincompatible T and B lymphocytes: the H-2 gene complex determines successful physiologic lymphocyte interactions. PNAS 70:2624–28
     [Google Scholar]
  32. 32. 
    Kindred B. 1971. Antibody response in genetically thymus-less nude mice injected with normal thymus cells. J. Immunol. 107:1291–95
     [Google Scholar]
  33. 33. 
    Klein J. 1986. Seeds of time: Fifty years ago Peter A. Gorer discovered the H-2 complex. Immunogenetics 24:331–38
     [Google Scholar]
  34. 34. 
    McDevitt HO, Tyan ML. 1968. Genetic control of the antibody response in inbred mice: transfer of response by spleen cells and linkage to the major histocompatibility (H-2) locus. J. Exp. Med. 128:1–11
     [Google Scholar]
  35. 35. 
    Doherty PC, Zinkernagel RM. 1975. H-2 compatibility is required for T-cell-mediated lysis of target cells infected with lymphocytic choriomeningitis virus. J. Exp. Med. 141:502–7
     [Google Scholar]
  36. 36. 
    Zinkernagel RM, Doherty PC. 1974. Restriction of in vitro T cell-mediated cytotoxicity in lymphocytic choriomeningitis within a syngeneic or semiallogeneic system. Nature 248:701–2
     [Google Scholar]
  37. 37. 
    Bevan MJ. 1975. The major histocompatibility complex determines susceptibility to cytotoxic T cells directed against minor histocompatibility antigens. J. Exp. Med. 142:1349–64
     [Google Scholar]
  38. 38. 
    Shearer GM, Schmitt-Verhulst AM, Pettinelli CB, Miller MW, Gilheany PE 1979. H-2-linked genetic control of murine T-cell-mediated lympholysis to autologous cells modified with low concentrations of trinitrobenzene sulfonate. J. Exp. Med. 149:1407–23
     [Google Scholar]
  39. 39. 
    Gordon RD, Simpson E, Samelson LE 1975. In vitro cell-mediated immune responses to the male specific (H-Y) antigen in mice. J. Exp. Med. 142:1108–20
     [Google Scholar]
  40. 40. 
    Kappler JW, Marrack P. 1977. The role of H-2-linked genes in helper T-cell function. I. In vitro expression in B cells of immune response genes controlling helper T-cell activity. J. Exp. Med. 146:1748–64
     [Google Scholar]
  41. 41. 
    Kappler JW, Marrack PC. 1976. Helper T cells recognise antigen and macrophage surface components simultaneously. Nature 262:797–99
     [Google Scholar]
  42. 42. 
    Sprent J, von Boehmer H 1976. Helper function of T cells depleted of alloantigen-reactive lymphocytes by filtration through irradiated F1 hybrid recipients. I. Failure to collaborate with allogeneic B cells in a secondary response to sheep erythrocytes measured in vivo. J. Exp. Med. 144:617–26
     [Google Scholar]
  43. 43. 
    von Boehmer H, Hudson L, Sprent J 1975. Collaboration of histoincompatible T and B lymphocytes using cells from tetraparental bone marrow chimeras. J. Exp. Med. 142:989–97
     [Google Scholar]
  44. 44. 
    Zinkernagel RM, Callahan GN, Althage A, Cooper S, Klein PA, Klein J 1978. On the thymus in the differentiation of “H-2 self-recognition” by T cells: evidence for dual recognition?. J. Exp. Med. 147:882–96
     [Google Scholar]
  45. 45. 
    Harwell L, Skidmore B, Marrack P, Kappler J 1980. Concanavalin A-inducible, interleukin-2-producing T cell hybridoma. J. Exp. Med. 152:893–904
     [Google Scholar]
  46. 46. 
    Roehm NW, Marrack P, Kappler JW 1982. Antigen-specific, H-2-restricted helper T cell hybridomas. J. Exp. Med. 156:191–204
     [Google Scholar]
  47. 47. 
    Walker E, Warner NL, Chesnut R, Kappler J, Marrack P 1982. Antigen-specific: I region-restricted interactions in vitro between tumor cell lines and T cell hybridomas. J. Immunol. 128:2164–69
     [Google Scholar]
  48. 48. 
    Hulbert C, Riseili B, Rojas M, Thomas JW 2001. B cell specificity contributes to the outcome of diabetes in nonobese diabetic mice. J. Immunol. 167:5535–38
     [Google Scholar]
  49. 49. 
    Chambers SA, Isenberg D. 2005. Anti-B cell therapy (rituximab) in the treatment of autoimmune diseases. Lupus 14:210–14
     [Google Scholar]
  50. 50. 
    O'Neill SK, Glant TT, Finnegan A 2007. The role of B cells in animal models of rheumatoid arthritis. Front. Biosci. 12:1722–36
     [Google Scholar]
  51. 51. 
    Kappler JW, Skidmore B, White J, Marrack P 1981. Antigen-inducible, H-2-restricted, interleukin-2-producing T cell hybridomas: lack of independent antigen and H-2 recognition. J. Exp. Med. 153:1198–214
     [Google Scholar]
  52. 52. 
    Feldmann M. 1972. Cell interactions in the immune response in vitro. V. Specific collaboration via complexes of antigen and thymus-derived cell immunoglobulin. J. Exp. Med. 136:737–60
     [Google Scholar]
  53. 53. 
    Cone RE, Marchalonis JJ. 1974. Surface proteins of thymus-derived lymphocytes and bone-marrow-derived lymphocytes: selective isolation of immunoglobulin and the theta-antigen by non-ionic detergents. Biochem. J. 140:345–54
     [Google Scholar]
  54. 54. 
    Binz H, Frischknecht H, Mercolli C, Dunst S, Wigzell H 1979. Binding of purified, soluble major histocompatibility complex polypeptide chains onto isolated T-cell receptors. I. Reactivity against allo- and self-determinants. J. Exp. Med. 150:1084–95
     [Google Scholar]
  55. 55. 
    Haskins K, Kubo R, White J, Pigeon M, Kappler J, Marrack P 1983. The major histocompatibility complex-restricted antigen receptor on T cells. I. Isolation with a monoclonal antibody. J. Exp. Med. 157:1149–69
     [Google Scholar]
  56. 56. 
    Kappler J, Kubo R, Haskins K, White J, Marrack P 1983. The mouse T cell receptor: comparison of MHC-restricted receptors on two T cell hybridomas. Cell 34:727–37
     [Google Scholar]
  57. 57. 
    Allison JP, McIntyre BW, Bloch D 1982. Tumor-specific antigen of murine T-lymphoma defined with monoclonal antibody. J. Immunol. 129:2293–300
     [Google Scholar]
  58. 58. 
    Meuer SC, Acuto O, Hussey RE, Hodgdon JC, Fitzgerald KA et al. 1983. Evidence for the T3-associated 90K heterodimer as the T-cell antigen receptor. Nature 303:808–10
     [Google Scholar]
  59. 59. 
    Yanagi Y, Yoshikai Y, Leggett K, Clark SP, Aleksander I, Mak TW 1984. A human T cell-specific cDNA clone encodes a protein having extensive homology to immunoglobulin chains. Nature 308:145–49
     [Google Scholar]
  60. 60. 
    Hedrick SM, Cohen DI, Nielsen EA, Davis MM 1984. Isolation of cDNA clones encoding T cell-specific membrane-associated proteins. Nature 308:149–53
     [Google Scholar]
  61. 61. 
    Hozumi N, Tonegawa S. 1976. Evidence for somatic rearrangement of immunoglobulin genes coding for variable and constant regions. PNAS 73:3628–32
     [Google Scholar]
  62. 62. 
    Chien Y, Becker DM, Lindsten T, Okamura M, Cohen DI, Davis MM 1984. A third type of murine T-cell receptor gene. Nature 312:31–35
     [Google Scholar]
  63. 63. 
    Sim GK, Yague J, Nelson J, Marrack P, Palmer E et al. 1984. Primary structure of human T-cell receptor alpha-chain. Nature 312:771–75
     [Google Scholar]
  64. 64. 
    Hannum CH, Kappler JW, Trowbridge IS, Marrack P, Freed JH 1984. Immunoglobulin-like nature of the alpha-chain of a human T-cell antigen/MHC receptor. Nature 312:65–67
     [Google Scholar]
  65. 65. 
    Saito H, Kranz DM, Takagaki Y, Hayday AC, Eisen HN, Tonegawa S 1984. Complete primary structure of a heterodimeric T-cell receptor deduced from cDNA sequences. Nature 309:757–62
     [Google Scholar]
  66. 66. 
    Hayday AC, Saito H, Gillies SD, Kranz DM, Tanigawa G et al. 1985. Structure, organization, and somatic rearrangement of T cell gamma genes. Cell 40:259–69
     [Google Scholar]
  67. 67. 
    Saito H, Kranz DM, Takagaki Y, Hayday AC, Eisen HN, Tonegawa S 1984. A third rearranged and expressed gene in a clone of cytotoxic T lymphocytes. Nature 312:36–40
     [Google Scholar]
  68. 68. 
    Chien YH, Iwashima M, Kaplan KB, Elliott JF, Davis MM 1987. A new T-cell receptor gene located within the alpha locus and expressed early in T-cell differentiation. Nature 327:677–82
     [Google Scholar]
  69. 69. 
    Unanue ER, Askonas BA. 1968. Persistence of immunogenicity of antigen after uptake by macrophages. J. Exp. Med. 127:915–26
     [Google Scholar]
  70. 70. 
    Humphrey JH, Askonas BA, Auzins I, Schechter I, Sela M 1967. The localization of antigen in lymph nodes and its relation to specific antibody-producing cells. II. Comparison of iodine-125 and tritium labels. Immunology 13:71–86
     [Google Scholar]
  71. 71. 
    Unanue ER, Askonas BA, Allison AC 1969. A role of macrophages in the stimulation of immune responses by adjuvants. J. Immunol. 103:71–78
     [Google Scholar]
  72. 72. 
    Ziegler HK, Unanue ER. 1982. Decrease in macrophage antigen catabolism caused by ammonia and chloroquine is associated with inhibition of antigen presentation to T cells. PNAS 79:175–78
     [Google Scholar]
  73. 73. 
    Ziegler K, Unanue ER. 1981. Identification of a macrophage antigen-processing event required for I-region-restricted antigen presentation to T lymphocytes. J. Immunol. 127:1869–75
     [Google Scholar]
  74. 74. 
    Chesnut RW, Colon SM, Grey HM 1982. Requirements for the processing of antigens by antigen-presenting B cells. I. Functional comparison of B cell tumors and macrophages. J. Immunol. 129:2382–88
     [Google Scholar]
  75. 75. 
    Shimonkevitz R, Colon S, Kappler JW, Marrack P, Grey HM 1984. Antigen recognition by H-2-restricted T cells. II. A tryptic ovalbumin peptide that substitutes for processed antigen. J. Immunol. 133:2067–74
     [Google Scholar]
  76. 76. 
    Carbone FR, Moore MW, Sheil JM, Bevan MJ 1988. Induction of cytotoxic T lymphocytes by primary in vitro stimulation with peptides. J. Exp. Med. 167:1767–79
     [Google Scholar]
  77. 77. 
    Townsend AR, Bastin J, Gould K, Brownlee GG 1986. Cytotoxic T lymphocytes recognize influenza haemagglutinin that lacks a signal sequence. Nature 324:575–77
     [Google Scholar]
  78. 78. 
    Buus S, Sette A, Colon SM, Jenis DM, Grey HM 1986. Isolation and characterization of antigen-Ia complexes involved in T cell recognition. Cell 47:1071–77
     [Google Scholar]
  79. 79. 
    Buus S, Colon S, Smith C, Freed JH, Miles C, Grey HM 1986. Interaction between a “processed” ovalbumin peptide and Ia molecules. PNAS 83:3968–71
     [Google Scholar]
  80. 80. 
    Babbitt BP, Matsueda G, Haber E, Unanue ER, Allen PM 1986. Antigenic competition at the level of peptide-Ia binding. PNAS 83:4509–13
     [Google Scholar]
  81. 81. 
    Rudensky A, Preston-Hurlburt P, Hong SC, Barlow A, Janeway CA Jr 1991. Sequence analysis of peptides bound to MHC class II molecules. Nature 353:622–27
     [Google Scholar]
  82. 82. 
    Bjorkman PJ, Saper MA, Samraoui B, Bennett WS, Strominger JL, Wiley DC 1987. The foreign antigen binding site and T cell recognition regions of class I histocompatibility antigens. Nature 329:512–18
     [Google Scholar]
  83. 83. 
    Garcia KC, Degano M, Stanfield RL, Brunmark A, Jackson MR et al. 1996. An αβ T cell receptor structure at 2.5 Å and its orientation in the TCR-MHC complex. Science 274:209–19
     [Google Scholar]
  84. 84. 
    Reinherz EL, Kung PC, Goldstein G, Schlossman SF 1979. Separation of functional subsets of human T cells by a monoclonal antibody. PNAS 76:4061–65
     [Google Scholar]
  85. 85. 
    Zarling JM, Kung PC. 1980. Monoclonal antibodies which distinguish between human NK cells and cytotoxic T lymphocytes. Nature 288:394–96
     [Google Scholar]
  86. 86. 
    Dialynas DP, Quan ZS, Wall KA, Pierres A, Quintans J et al. 1983. Characterization of the murine T cell surface molecule, designated L3T4, identified by monoclonal antibody GK1.5: similarity of L3T4 to the human Leu-3/T4 molecule. J. Immunol. 131:2445–51
     [Google Scholar]
  87. 87. 
    Sarmiento M, Glasebrook AL, Fitch FW 1980. IgG or IgM monoclonal antibodies reactive with different determinants on the molecular complex bearing Lyt 2 antigen block T cell-mediated cytolysis in the absence of complement. J. Immunol. 125:2665–72
     [Google Scholar]
  88. 88. 
    Ledbetter JA, Rouse RV, Micklem HS, Herzenberg LA 1980. T cell subsets defined by expression of Lyt-1,2,3 and Thy-1 antigens: Two-parameter immunofluorescence and cytotoxicity analysis with monoclonal antibodies modifies current views. J. Exp. Med. 152:280–95
     [Google Scholar]
  89. 89. 
    Biddison WE, Rao PE, Talle MA, Goldstein G, Shaw S 1982. Possible involvement of the OKT4 molecule in T cell recognition of class II HLA antigens: evidence from studies of cytotoxic T lymphocytes specific for SB antigens. J. Exp. Med. 156:1065–76
     [Google Scholar]
  90. 90. 
    Biddison WE, Sharrow SO, Shearer GM 1981. T cell subpopulations required for the human cytotoxic T lymphocyte response to influenza virus: evidence for T cell help. J. Immunol. 127:487–91
     [Google Scholar]
  91. 91. 
    Swain SL. 1981. Significance of Lyt phenotypes: Lyt2 antibodies block activities of T cells that recognize class 1 major histocompatibility complex antigens regardless of their function. PNAS 78:7101–5
     [Google Scholar]
  92. 92. 
    Swain SL, Dialynas DP, Fitch FW, English M 1984. Monoclonal antibody to L3T4 blocks the function of T cells specific for class 2 major histocompatibility complex antigens. J. Immunol. 132:1118–23
     [Google Scholar]
  93. 93. 
    Dalgleish AG, Beverley PC, Clapham PR, Crawford DH, Greaves MF, Weiss RA 1984. The CD4 (T4) antigen is an essential component of the receptor for the AIDS retrovirus. Nature 312:763–67
     [Google Scholar]
  94. 94. 
    Kisielow P, Leiserson W, Von Boehmer H 1984. Differentiation of thymocytes in fetal organ culture: analysis of phenotypic changes accompanying the appearance of cytolytic and interleukin 2-producing cells. J. Immunol. 133:1117–23
     [Google Scholar]
  95. 95. 
    Mathieson BJ, Fowlkes BJ. 1984. Cell surface antigen expression on thymocytes: development and phenotypic differentiation of intrathymic subsets. Immunol. Rev. 82:141–73
     [Google Scholar]
  96. 96. 
    Scollay R, Bartlett P, Shortman K 1984. T cell development in the adult murine thymus: changes in the expression of the surface antigens Ly2, L3T4 and B2A2 during development from early precursor cells to emigrants. Immunol. Rev. 82:79–103
     [Google Scholar]
  97. 97. 
    Haskins K, Hannum C, White J, Roehm N, Kubo R et al. 1984. The antigen-specific, major histocompatibility complex-restricted receptor on T cells. VI. An antibody to a receptor allotype. J. Exp. Med. 160:452–71
     [Google Scholar]
  98. 98. 
    Kappler JW, Staerz U, White J, Marrack PC 1988. Self-tolerance eliminates T cells specific for Mls-modified products of the major histocompatibility complex. Nature 332:35–40
     [Google Scholar]
  99. 99. 
    Roehm N, Herron L, Cambier J, DiGuisto D, Haskins K et al. 1984. The major histocompatibility complex-restricted antigen receptor on T cells: distribution on thymus and peripheral T cells. Cell 38:577–84
     [Google Scholar]
  100. 100. 
    Lederberg J. 1959. Genes and antibodies. Science 129:1649–53
     [Google Scholar]
  101. 101. 
    Nossal GJ, Pike BL. 1975. Evidence for the clonal abortion theory of B-lymphocyte tolerance. J. Exp. Med. 141:904–17
     [Google Scholar]
  102. 102. 
    Kappler JW, Roehm N, Marrack P 1987. T cell tolerance by clonal elimination in the thymus. Cell 49:273–80
     [Google Scholar]
  103. 103. 
    Kisielow P, Bluthmann H, Staerz UD, Steinmetz M, von Boehmer H 1988. Tolerance in T-cell-receptor transgenic mice involves deletion of nonmature CD4+8+ thymocytes. Nature 333:742–46
     [Google Scholar]
  104. 104. 
    Festenstein H. 1973. Immunogenetic and biological aspects of in vitro lymphocyte allotransformation (MLR) in the mouse. Transplant. Rev. 15:62–88
     [Google Scholar]
  105. 105. 
    Sprent J, von Boehmer H 1976. Activation of T lymphocytes to M locus determinants in vivo. I. Quantitation of T cell proliferation and migration into thoracic duct lymph. Eur. J. Immunol. 6:352–58
     [Google Scholar]
  106. 106. 
    Bishop C, Festenstein H, Taylor B 1976. M-locus: linkage studies [proceedings]. Folia Biol 22:422
     [Google Scholar]
  107. 107. 
    Lindahl KF, Byers DE, Dabhi VM, Hovik R, Jones EP et al. 1997. H2-M3, a full-service class Ib histocompatibility antigen. Annu. Rev. Immunol. 15:851–79
     [Google Scholar]
  108. 108. 
    Choi YW, Henrard D, Lee I, Ross SR 1987. The mouse mammary tumor virus long terminal repeat directs expression in epithelial and lymphoid cells of different tissues in transgenic mice. J. Virol. 61:3013–19
     [Google Scholar]
  109. 109. 
    Choi Y, Kappler JW, Marrack P 1991. A superantigen encoded in the open reading frame of the 3′ long terminal repeat of mouse mammary tumour virus. Nature 350:203–7
     [Google Scholar]
  110. 110. 
    Winslow GM, Scherer MT, Kappler JW, Marrack P 1992. Detection and biochemical characterization of the mouse mammary tumor virus 7 superantigen (Mls-1a). Cell 71:719–30
     [Google Scholar]
  111. 111. 
    Dyson PJ, Knight AM, Fairchild S, Simpson E, Tomonari K 1991. Genes encoding ligands for deletion of Vβ11 T cells cosegregate with mammary tumour virus genomes. Nature 349:531–32
     [Google Scholar]
  112. 112. 
    Frankel WN, Rudy C, Coffin JM, Huber BT 1991. Linkage of Mls genes to endogenous mammary tumour viruses of inbred mice. Nature 349:526–28
     [Google Scholar]
  113. 113. 
    Woodland DL, Happ MP, Gollob KJ, Palmer E 1991. An endogenous retrovirus mediating deletion of αβ T cells?. Nature 349:529–30
     [Google Scholar]
  114. 114. 
    Vella A, Teague TK, Ihle J, Kappler J, Marrack P 1997. Interleukin 4 (IL-4) or IL-7 prevents the death of resting T cells: Stat6 is probably not required for the effect of IL-4. J. Exp. Med. 186:325–30
     [Google Scholar]
  115. 115. 
    Ku CC, Murakami M, Sakamoto A, Kappler J, Marrack P 2000. Control of homeostasis of CD8+ memory T cells by opposing cytokines. Science 288:675–78
     [Google Scholar]
  116. 116. 
    Tan JT, Ernst B, Kieper WC, LeRoy E, Sprent J, Surh CD 2002. Interleukin (IL)-15 and IL-7 jointly regulate homeostatic proliferation of memory phenotype CD8+ cells but are not required for memory phenotype CD4+ cells. J. Exp. Med. 195:1523–32
     [Google Scholar]
  117. 117. 
    Pape KA, Khoruts A, Mondino A, Jenkins MK 1997. Inflammatory cytokines enhance the in vivo clonal expansion and differentiation of antigen-activated CD4+ T cells. J. Immunol. 159:591–98
     [Google Scholar]
  118. 118. 
    Altman JD, Moss PA, Goulder PJ, Barouch DH, McHeyzer-Williams MG et al. 1996. Phenotypic analysis of antigen-specific T lymphocytes. Science 274:94–96
     [Google Scholar]
  119. 119. 
    Kawabe Y, Ochi A. 1991. Programmed cell death and extrathymic reduction of Vβ8+ CD4+ T cells in mice tolerant to Staphylococcusaureus enterotoxin B. Nature 349:245–48
     [Google Scholar]
  120. 120. 
    Webb SR, O'Rourke AM, Sprent J 1992. Factors influencing the fate of T cells responding to Mls antigens. Semin. Immunol. 4:329–36
     [Google Scholar]
  121. 121. 
    Marrack P, Hugo P, McCormack J, Kappler J 1993. Death and T cells. Immunol. Rev. 133:119–29
     [Google Scholar]
  122. 122. 
    O'Connor L, Strasser A, O'Reilly LA, Hausmann G, Adams JM et al. 1998. Bim: a novel member of the Bcl-2 family that promotes apoptosis. EMBO J 17:384–95
     [Google Scholar]
  123. 123. 
    Hildeman DA, Zhu Y, Mitchell TC, Bouillet P, Strasser A et al. 2002. Activated T cell death in vivo mediated by proapoptotic Bcl-2 family member Bim. Immunity 16:759–67
     [Google Scholar]
  124. 124. 
    Janeway CA Jr 1993. How the immune system recognizes invaders. Sci. Am. 269:72–79
     [Google Scholar]
  125. 125. 
    Medzhitov R, Janeway CA Jr 1997. Innate immunity: the virtues of a nonclonal system of recognition. Cell 91:295–98
     [Google Scholar]
  126. 126. 
    Rubtsov AV, Rubtsova K, Fischer A, Meehan RT, Gillis JZ et al. 2011. Toll-like receptor 7 (TLR7)-driven accumulation of a novel CD11c+ B-cell population is important for the development of autoimmunity. Blood 118:1305–15
     [Google Scholar]
  127. 127. 
    Rubtsova K, Rubtsov AV, Thurman JM, Mennona JM, Kappler JW, Marrack P 2017. B cells expressing the transcription factor T-bet drive lupus-like autoimmunity. J. Clin. Investig. 127:1392–404
     [Google Scholar]
  128. 128. 
    Isnardi I, Ng YS, Menard L, Meyers G, Saadoun D et al. 2010. Complement receptor 2/CD21− human naive B cells contain mostly autoreactive unresponsive clones. Blood 115:5026–36
     [Google Scholar]
  129. 129. 
    Takahashi K, Kozono Y, Waldschmidt TJ, Berthiaume D, Quigg RJ et al. 1997. Mouse complement receptors type 1 (CR1;CD35) and type 2 (CR2;CD21): expression on normal B cell subpopulations and decreased levels during the development of autoimmunity in MRL/lpr mice. J. Immunol. 159:1557–69
     [Google Scholar]
  130. 130. 
    Holers VM, Boackle SA. 2004. Complement receptor 2 and autoimmunity. Curr. Dir. Autoimmun. 7:33–48
     [Google Scholar]
  131. 131. 
    Arumugakani G, Wood PM, Carter CR 2010. Frequency of Treg cells is reduced in CVID patients with autoimmunity and splenomegaly and is associated with expanded CD21lo B lymphocytes. J. Clin. Immunol. 30:292–300
     [Google Scholar]
  132. 132. 
    Azizi G, Abolhassani H, Kiaee F, Tavakolinia N, Rafiemanesh H et al. 2018. Autoimmunity and its association with regulatory T cells and B cell subsets in patients with common variable immunodeficiency. Allergol. Immunopathol. 46:127–35
     [Google Scholar]
  133. 133. 
    Aranburu A, Hook N, Gerasimcik N, Corleis B, Ren W et al. 2018. Age-associated B cells expanded in autoimmune mice are memory cells sharing H-CDR3-selected repertoires. Eur. J. Immunol. 48:509–21
     [Google Scholar]
  134. 134. 
    Ferre EM, Rose SR, Rosenzweig SD, Burbelo PD, Romito KR et al. 2016. Redefined clinical features and diagnostic criteria in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy. JCI Insight 1:e88782
     [Google Scholar]
  135. 135. 
    Warnatz K, Wehr C, Drager R, Schmidt S, Eibel H et al. 2002. Expansion of CD19hiCD21lo/neg B cells in common variable immunodeficiency (CVID) patients with autoimmune cytopenia. Immunobiology 206:502–13
     [Google Scholar]
  136. 136. 
    Astorri E, Bombardieri M, Gabba S, Peakman M, Pozzilli P, Pitzalis C 2010. Evolution of ectopic lymphoid neogenesis and in situ autoantibody production in autoimmune nonobese diabetic mice: cellular and molecular characterization of tertiary lymphoid structures in pancreatic islets. J. Immunol. 185:3359–68
     [Google Scholar]
  137. 137. 
    Glauzy S, Sng J, Bannock JM, Gottenberg JE, Korganow AS et al. 2017. Defective early B cell tolerance checkpoints in Sjogren's syndrome patients. Arthritis Rheumatol 69:2203–8
     [Google Scholar]
  138. 138. 
    Winslow GM, Papillion AM, Kenderes KJ, Levack RC 2017. CD11c+ T-bet+ memory B cells: immune maintenance during chronic infection and inflammation. ? Cell Immunol 321:8–17
     [Google Scholar]
  139. 139. 
    Swain SL, Kugler-Umana O, Kuang Y, Zhang W 2017. The properties of the unique age-associated B cell subset reveal a shift in strategy of immune response with age. Cell Immunol 321:52–60
     [Google Scholar]
  140. 140. 
    Jerne NK. 1971. The somatic generation of immune recognition. Eur. J. Immunol. 1:1–9
     [Google Scholar]
  141. 141. 
    Fink PJ, Bevan MJ. 1978. H-2 antigens of the thymus determine lymphocyte specificity. J. Exp. Med. 148:766–75
     [Google Scholar]
  142. 142. 
    Merkenschlager M, Graf D, Lovatt M, Bommhardt U, Zamoyska R, Fisher AG 1997. How many thymocytes audition for selection?. J. Exp. Med. 186:1149–58
     [Google Scholar]
  143. 143. 
    Zerrahn J, Held W, Raulet DH 1997. The MHC reactivity of the T cell repertoire prior to positive and negative selection. Cell 88:627–36
     [Google Scholar]
  144. 144. 
    Blackman M, Yague J, Kubo R, Gay D, Coleclough C et al. 1986. The T cell repertoire may be biased in favor of MHC recognition. Cell 47:349–57
     [Google Scholar]
  145. 145. 
    Van Laethem F, Tikhonova AN, Pobezinsky LA, Tai X, Kimura MY et al. 2013. Lck availability during thymic selection determines the recognition specificity of the T cell repertoire. Cell 154:1326–41
     [Google Scholar]
  146. 146. 
    Huseby ES, White J, Crawford F, Vass T, Becker D et al. 2005. How the T cell repertoire becomes peptide and MHC specific. Cell 122:247–60
     [Google Scholar]
  147. 147. 
    Scott-Browne JP, White J, Kappler JW, Gapin L, Marrack P 2009. Germline-encoded amino acids in the αβ T-cell receptor control thymic selection. Nature 458:1043–46
     [Google Scholar]
  148. 148. 
    Ge C, Holmdahl R. 2019. The structure, specificity and function of anti-citrullinated protein antibodies. Nat. Rev. Rheumatol. 15:503–8
     [Google Scholar]
  149. 149. 
    Holers VM, Demoruelle MK, Kuhn KA, Buckner JH, Robinson WH et al. 2018. Rheumatoid arthritis and the mucosal origins hypothesis: protection turns to destruction. Nat. Rev. Rheumatol. 14:542–57
     [Google Scholar]
  150. 150. 
    Stadinski BD, Delong T, Reisdorph N, Reisdorph R, Powell RL et al. 2010. Chromogranin A is an autoantigen in type 1 diabetes. Nat. Immunol. 11:225–31
     [Google Scholar]
  151. 151. 
    Stadinski BD, Zhang L, Crawford F, Marrack P, Eisenbarth GS, Kappler JW 2010. Diabetogenic T cells recognize insulin bound to IAg7 in an unexpected, weakly binding register. PNAS 107:10978–83
     [Google Scholar]
  152. 152. 
    Wang Y, Sosinowski T, Novikov A, Crawford F, Neau DB et al. 2018. C-terminal modification of the insulin B:11–23 peptide creates superagonists in mouse and human type 1 diabetes. PNAS 115:162–67
     [Google Scholar]
/content/journals/10.1146/annurev-immunol-072319-033325
Loading
  • Article Type: Review Article

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error