Advertisement

Cellular Detection of Human Class II Antigens: Delineation of a Novel HLA-DP-like Suppressor Restriction System DY, the Sequential Expression of Class II Antigens, and a Pronounced Functional Flexibility of Class II Alloproliferative T Cell Clones

  • P. Wernet
  • G. Pawelec
  • E. M. Schneider

Abstract

HLA class II gene products, encoded on the short arm of chromosome 6 in the region of 6p21.33 [1], are expressed with limited tissue distribution on the surfaces of immunologically active cells, predominantly B lymphocytes, monocytes, dendritic cells, and macrophages [2, 3]. They are in addition synthesized and expressed by certain other types of cells, notably activated T lymphocytes [4], and various kinds of endothelia and epithelia, especially after induction by agents such as gamma-interferon [5]. Class II antigens are of critical importance for the initiation of immune responses, since at least the majority of T helper cells fails to recognize antigen unless both class II molecules and antigen are available on the surface of the same antigen-presenting cell [6]. Allogeneic class II products stimulate T cell proliferative responses in the apparent absence of additional antigen by virtue of their polymorphism. Although the basis of alloreactivity is not fully understood, the restriction elements for antigen presentation correlate closely with the class II specificities defined by alloreactive T cells, making it fair to assume that the same gene products, and possibly even identical epitopes, are involved in both recognition systems [7, 8].

Keywords

Cell Clone Bone Marrow Trans Restriction Element Lymphocyte Clone Homozygous Typing Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Spring B, Fonatsch C, Müller C, Pawelec G, Kömpf J, Wernet P, Ziegler A (1985) Refinement of HLA gene mapping with induced B cell line mutants. Immunogenetics 21:277–291PubMedCrossRefGoogle Scholar
  2. 2.
    Frelinger J A (1982) Tissue distribution and cellular expression of la antigens. In: Ferrone S, David CS (eds) la antigens. CRC Press, Boca Raton, pp 37–54Google Scholar
  3. 3.
    Wernet P (1976) Human la-type alloantigens: methods of detection, aspects of chemistry and biology, markers for disease states. Transplant Rev 30:271–298PubMedGoogle Scholar
  4. 4.
    Charron DJ, Engleman EG, Benike CJ, McDevitt HO (1980) la antigens on alloreactive T cells in man detected by monoclonal antibodies. Evidence for synthesis of HLA-D/DR molecules of the responder type. J Exp Med 152:127s–136sPubMedGoogle Scholar
  5. 5.
    Steeg PS, Moore RN, Johnson HM, Oppenheim JS (1982) Regulation of murine macrophage la antigen expression by a lymphokine with immune interferon activity. J Exp Med 156:1780–1793PubMedCrossRefGoogle Scholar
  6. 6.
    Thorsby E, Berle E, Nousiainen H (1982) HLA-D region molecules restrict proliferative responses to antigen. Immunol Rev 66:39–56PubMedCrossRefGoogle Scholar
  7. 7.
    Qvigstad E, Thorsby E, Reinsmoen NL, Bach FH (1984) Close association between the Dwl4 (LD40) subtype of HLA-DR4 and a restriction element for antigen-specific T cell clones. Immunogenetics 20:583–588PubMedCrossRefGoogle Scholar
  8. 8.
    Fleischer B, Blaurock M, Wernet P, Pawelec G (1984) Restriction of human influenza A virus-specific T cell clones by HTC-defined subtypes of HLA-Dw6. In: Albert ED, Baur MP, Mayr WR (eds) Histocompatibility Testing 1984. Springer, Berlin Heidelberg New York Tokyo, pp 623–626Google Scholar
  9. 9.
    Bain B, Vas MR, Lowenstein L (1964) The development of large immature mononuclear cells in mixed leukocyte cultures. Blood 23:108–116PubMedGoogle Scholar
  10. 10.
    Yunis EJ, Amos DB (1971) Three closely linked genetic systems relevant to transplantation. Proc Natl Acad Sci USA 68:3031–3035PubMedCrossRefGoogle Scholar
  11. 11.
    Bradley BA, Edwards JM, Dunn DC, Calne RY (1972) Quantitation of mixed lymphocyte reaction by gene dose phenomenon. Nature 240:54–56Google Scholar
  12. 12.
    Thorsby E, Piazza A (1975) Joint Report. II. Typing for HLA-D (LD-1 or MLC) determinants. In: Kissmeyer-Nielsen F (ed) Histocompatibility Testing 1975. Munksgaard, Copenhagen, pp 414–458Google Scholar
  13. 13.
    Carlsson B, Böhme J, Kalm B, Lundgren G, Möller E, Persson P, Petersen PA, Rask L, Wallin J (1984) HLA-DR and DQ studied with genomic blotting in diabetic families and transplant donor-recipient pairs. In: Albert ED, Baur MP, Mayr WR (eds) Histocompatibility Testing 1984. Springer, Berlin Heidelberg New York Tokyo, p 589Google Scholar
  14. 14.
    Fradelizi D, Dausset J (1975) Mixed lymphocyte reactivity of human lymphocytes primed in vitro. I. Secondary responses to allogeneic lymphocytes. Eur J Immunol 5:295–301PubMedCrossRefGoogle Scholar
  15. 15.
    Sheehy MJ, Sondel PM, Bach ML, Wank R, Bach FH (1975) HL-A LD (lymphocyte defined) typing: a rapid assay with primed lymphocytes. Science 188:1308–1310PubMedCrossRefGoogle Scholar
  16. 16.
    Alter BJ, Bach FH, Jaramillo S, Wernet P (1977) Typing an unrelated panel with PLT cells: association with Dw clusters. Scand J Immunol 6:485–489CrossRefGoogle Scholar
  17. 17.
    Shaw S, Johnson AH, Shearer GM (1980) Evidence for a new segregant series of B cell antigens that are encoded in the HLA-D region and that stimulate secondary allogeneic proliferative and cytotoxic responses. J Exp Med 152:565–580PubMedCrossRefGoogle Scholar
  18. 18.
    Bach FH, Inouye H, Hank J A, Alter BJ (1979) Human T lymphocyte clones reactive in primed lymphocyte typing and cytotoxicity. Nature 281:307–309PubMedCrossRefGoogle Scholar
  19. 19.
    Pawelec G, Wernet P (1980) Restimulation properties of human alloreactive cloned T-cell lines. Dissection of HLA-D-region alleles in population studies and family segregation analyses. Immunogenetics 11:507–519PubMedCrossRefGoogle Scholar
  20. 20.
    Inouye H, Hank JA, Chardonnens X, Segall M, Alter BJ, Bach FH (1980) Cloned primed lymphocyte test reagents in the dissection of HLA-D. J Exp Med 152:143s–155sPubMedGoogle Scholar
  21. 21.
    Duquesnoy RJ, Zeevi A (1983) Immunogenetic analysis of the HLA complex with T cell clones. Hum Immunol 8:17–23PubMedCrossRefGoogle Scholar
  22. 22.
    Pawelec G (1983) Allogeneically primed T lymphocyte clones in the analysis of lymphocyte stimulatory determinants. Hum Immunol 8:239–247PubMedCrossRefGoogle Scholar
  23. 23.
    Eckels DD, Hartzman RJ (1982) Characterisation of human T-lymphocyte clones (TLCs) specific for HLA-region gene products. Immunogenetics 16:117–133PubMedCrossRefGoogle Scholar
  24. 24.
    Zeevi A, Scheffel C, Annen K, Bass G, Marrari M, Duquesnoy RJ (1982) Association of PLT specificity of alloreactive lymphocyte clones with HLA-DR, MB, and MT determinants. Immunogenetics 16:209–218.23PubMedCrossRefGoogle Scholar
  25. 25.
    Zeevi A, Duquesnoy RJ (1983) PLT specificity of alloreactive lymphocyte clones for HLA-B locus determinants. Proc Natl Acad Sci USA 80:1440–1444PubMedCrossRefGoogle Scholar
  26. 26.
    Reinsmoen NL, Anichini A, Bach FH (1983) Clonal analysis of T lymphocytes responding to an isolated class I disparity. Hum Immunol 8:195–206PubMedCrossRefGoogle Scholar
  27. 27.
    Pawelec G, Shaw S, Wernet P (1982) Analysis of the HLA-linked SB gene system with cloned and uncloned alloreactive T-cell lines. Immunogenetics 15:187–198PubMedGoogle Scholar
  28. 28.
    Bach FH, Reinsmoen NL (1982) Cloned cellular reagents to define antigens encoded between HLA-DR and glyoxylase. Hum Immunol 5:133–138PubMedCrossRefGoogle Scholar
  29. 29.
    Pawelec G, Shaw S, Schneider M, Blaurock M, Frauer M, Brackertz D, Wernet P (1982) Population studies of HLA-linked SB antigens and their relative importance in MLC typing. Analysis of HLA-D homozygous typing cells and normal heterozygous populations. Hum Immunol 5:215–223PubMedCrossRefGoogle Scholar
  30. 30.
    Wernet P, Shaw S, Brautbar C, Westphal E, Pawelec G (1983) SB types of HLA-D homozygous typing cells. Immunogenetics 18:547–551PubMedCrossRefGoogle Scholar
  31. 31.
    Spits H, Borst J, Giphart M, Coligan J, Terhorst C, de Vries JE (1984) HLA-DC can serve as recognition elements for human cytotoxic T lymphocytes. Eur J Immunol 14:299–304PubMedCrossRefGoogle Scholar
  32. 32.
    Anichini A, Bach FH (1984) HLA-Dw/LD directed cytotoxic T cell clones. Hum Immunol 10:153–164PubMedCrossRefGoogle Scholar
  33. 33.
    Ohta N, Anichini A, Reinsmoen NL, Strassmann G, Wernet P, Bach FH (1985) Analysis of human class II antigens by cloned cytolytic T cell reagents: a study using loss mutant lymphoblastoid cell lines and monoclonal antibodies detecting the HLA-DP product(s). Hum Immunol 13:21–32PubMedCrossRefGoogle Scholar
  34. 34.
    Eckels DD, Zeevi A, Beatty PG, Flomenberg N, Goyert S, Knowles RW, Mickelson E, Nepom G, Parham P, Pawelec G, Reinsmoen NL (1985) ASHI workshop summary report: structural and functional relationships of human class IIMHC molecules. Hum Immunol (in press)Google Scholar
  35. 35.
    Sheehy MJ, Quintieri FB, Yang SY, Alosco SM, Matsui Y, Yunis EJ, Gabbay KH (1984) HLA antigens of insulin-dependent diabetics. I. PLT colonies detecting DwlO and a new class II determinant distinct from HLA-D, DR, MB(DC), MT, and SB. Tissue Antigens 23:290–300PubMedCrossRefGoogle Scholar
  36. 36.
    Pawelec G, Wernet P, Rosenlund R, Blaurock M, Schneider EM (1984) Strong lym-phoproliferative suppressive function of clones specific for SB-like antigens. Hum Immunol 9:145–157PubMedCrossRefGoogle Scholar
  37. 37.
    Zeevi A, Duquesnoy RJ (1985) Recognition of major histocompatibility gene products by human alloreactive T cell clones. In: von Boehmer H, Haas W (eds) T cell clones. Elsevier, Amsterdam, pp 245–262Google Scholar
  38. 38.
    Pawelec G, Shaw S, Ziegler A, Miiller C, Wernet P (1982) Differential inhibition of HLA-D- or SB-directed secondary lymphoproliferative responses with monoclonal antibodies detecting human la-like determinants. J Immunol 129:1070–1075PubMedGoogle Scholar
  39. 39.
    Wernet P, Ziegler A, Shaw S, Blaurock M, Pawelec G (1983) Monoclonal antibodies against la-like antigens inhibiting HLA-D and/or SB-directed secondary proliferative responses. Transplant Proc 15:94–98Google Scholar
  40. 40.
    Crumpton MJ, Bodmer JG, Bodmer WF, Hayes JM, Lindsay J, Rudd CE (1984) Biochemistry of class II antigens: workshop report. In: Albert ED, Baur MP, Mayr WR (eds) Histocompatibility Testing 1984. Springer, Berlin Heidelberg New York Tokyo, pp 29–37Google Scholar
  41. 41.
    Pawelec G, Schneider EM, Wernet P (1985) HLA-DR-, MB- and novel DC-related determinants restrict purified protein derivative of tuberculin (PPD)-stimulated human T cell proliferation. Eur J Immunol 15:12–17PubMedCrossRefGoogle Scholar
  42. 42.
    Austin P, Trowsdale J, Rudd C, Bodmer W, Feldmann M, Lamb J (1985) Functional expression of HLA-DP genes transfected into mouse fibroblasts. Nature 313:61–64PubMedCrossRefGoogle Scholar
  43. 43.
    Moen T, de Preval C, Rabourdin-Combe C, Mach B, Gaudernack G, Bondevik E, Thorsby E (1984) Mouse L cells expressing human HLA-DR antigens after transfection with class II genes do not stimulate human T lymphocytes. In: Albert ED, Baur MP, Mayr WR (eds) Histocompatibility Testing 1984. Springer, Berlin Heidelberg New York Tokyo, pp 595–598Google Scholar
  44. 44.
    Rebai N, Malissen B, Pierres M, Accolla RS, Corte G, Mawas C (1983) Distinct HLA-DR epitopes and distinct families of HLA-DR molecules defined by 15 monoclonal antibodies (mAb) either anti-DR or allo-anti-Iak cross-reacting with human DR molecule. I. Cross-inhibition studies of mAb cell surface fixation and differential binding of mAb to detergent-solubilised HLA molecules immobilised to a solid phase by a first mAb. Eur J Immunol 13:106–111PubMedCrossRefGoogle Scholar
  45. 45.
    Beckman IGR, Bradley J, Brooks D, Zola H (1984) Delineation of serologically distinct monomorphic determinants of human MHC class II antigens: evidence of heterogeneity in their topographical distribution. Mol Immunol 21:205–214PubMedCrossRefGoogle Scholar
  46. 46.
    Charron DJ, Lotteau V, Turmel P (1984) Hybrid HLA-DC antigens provide molecular evidence for gene trans-complementation. Nature 312:157–159PubMedCrossRefGoogle Scholar
  47. 47.
    Lamb JR, Woody JN, Hartzman RJ, Eckels DD (1982) In vitro influenza virus-specific antibody production in man: antigen-specific and HLA-restricted induction of helper activity mediated by cloned human T lymphocytes. J Immunol 129:1465–1470PubMedGoogle Scholar
  48. 48.
    Qvigstad E, Moen E, Thorsby E (1984) T cell clones with similar antigen specificity may be restricted by DR, MT(DC) or SB class II HLA molecules. Immunogenetics 19:455–460PubMedCrossRefGoogle Scholar
  49. 49.
    Eckels DD, Lake P, Lamb JR, Johnson AH, Shaw S, Woody JN, Hartzman RJ (1983) SB-restricted presentation of influenza and herpes simplex virus-antigens to human T lymphocyte clones. Nature 301:716–718PubMedCrossRefGoogle Scholar
  50. 50.
    Rees ADM, Knott G, Lamb JR (1985) Antigen specific human T cell clones: heterogeneity of specificity and function. Behring Inst Mitt 77:75–81PubMedGoogle Scholar
  51. 51.
    Zeevi A, Chiu KM, Duquesnoy RJ (1982) Heterogeneity of cytolytic and suppressor clones of alloactivated cells generated from soft agar colonies. Hum Immunol 5:107–122PubMedCrossRefGoogle Scholar
  52. 52.
    Pawelec G, Schneider EM, Wernet P (1985) Function of alloproliferative clones correlates better with their class II recognitive specificity than with their cell surface pheno-type. Eur J Immunol 15:163–167PubMedCrossRefGoogle Scholar
  53. 53.
    Pawelec G, Schneider EM, Wernet P (1984) Cloned human T lymphocytes with lym-phostimulatory activity preferentially activate suppressor cells. Eur J Immunol 14:335–340PubMedCrossRefGoogle Scholar
  54. 54.
    Pawelec G, Wernet P (1985) Loss of alloreactivity associated with acquired suppressive and natural killer-like activities of aged T cell clones. In: Feldmann M, Lamb JR, Woody JN (eds) Human T cell clones: a modern approach to immunoregulation. Humana, Clifton, New Jersey p 327–339Google Scholar
  55. 55.
    Wernet P, Betsch C, Barth P, Jaramillo S, Schunter F, Waller HD, Wilms K (1977) Human la alloantigens as cell-differentiation markers of normal and pathological leukocyte surfaces. Scand J Immunol 6:563–574PubMedCrossRefGoogle Scholar
  56. 56.
    Mach B, de Preval C, Gorski J (1984) Molecular genetics of human class II genes and the regulation of their expression. In: Griscelli C, Vossen J (eds) Progress in immunodeficiency research and therapy, vol I. Elsevier, Amsterdam, pp 11–17Google Scholar
  57. 57.
    Newman RA, Delia B, Greaves MF, Navarrete C, Fainboim L, Festenstein H (1983) Differential expression of HLA-DR and DR-linked determinants on human leukemias and lymphoid cells. Eur J Immunol 13:172–177PubMedCrossRefGoogle Scholar
  58. 58.
    Wernet P, Müller CP, Ostendorf P (1984) Reactivity of lymphocytic and myelocytic leukemia blasts with monoclonal antibodies specific for the different human class II molecules. Dis Markers 2:449–459Google Scholar
  59. 59.
    Long EO, Mach B, Acolla RS (1984) la-negative B-cell variants reveal a coordinate regulation in the transcription of the HLA class II gene family. Immunogenetics 19:349–353PubMedCrossRefGoogle Scholar
  60. 60.
    Goyert SM, Shively JE, Silver J (1982) Biochemical characterization of a second family of human la antigens. HLA-DS, equivalent to murine I-A subregion molecules. J Exp Med 156:550–566PubMedCrossRefGoogle Scholar
  61. 61.
    Wang CY, Al-Katib A, Lane CL, Koznier B, Fu SM (1983) Induction of HLA-DC/DS (Leu 10) antigen expression by human precursor B cell lines. J Exp Med 158:1757–1762PubMedCrossRefGoogle Scholar
  62. 62.
    Sieff C, Bicknell D, Caine G, Robinson J, Lam G, Greaves MF (1982) Changes in cell surface antigen expression during hematopoietic differentiation. Blood 60:703–713PubMedGoogle Scholar
  63. 63.
    Barth P, Schunter F, Wilms K, Waller HD, Wernet P (1978) Classification of leukemic cells by la alloantigens and complement receptors. Bibl Haematologica 45:124–130Google Scholar
  64. 64.
    Gordon LI, Miller WJ, Branda RF, Zanjani ED, Jacob HS (1980) Regulation of ery-throid colony formation by bone marrow (BM) macrophages. Blood 55:1047–1050PubMedGoogle Scholar
  65. 65.
    Möller E, Carlsson B, Wallin J (1985) Distinct or overlapping functions of human class II genes? Scand J Immunol 20:483–487CrossRefGoogle Scholar
  66. 66.
    Van Voorhis WC, Hair LS, Steinman RM, Kaplan G (1982) Human dendritic cells. Enrichment and characterization from peripheral blood. J Exp Med 155:1172–1187PubMedCrossRefGoogle Scholar
  67. 67.
    Parwaresch MR, Radzun HJ, Feller AC, Peters K-P, Hansmann M-L (1983) Peroxi-dase-positive mononuclear leukocytes as possible precursors of human dendritic reticulum cells. J Immunol 131:2719–2725PubMedGoogle Scholar
  68. 68.
    Malissen B, Charmot D, Mawas C (1981) Expansion of human lymphocyte populations expressing specific immune reactivities. III. Specific colonies, either cytotoxic or proliferative, obtained from a population of responder cells primed in vitro. Preliminary immunogenetic analysis. Hum Immunol 2:1–13PubMedCrossRefGoogle Scholar
  69. 69.
    Effros RB, Walford RL (1984) T cell cultures and the Hayflick limit. Hum Immunol 9:49–65PubMedCrossRefGoogle Scholar
  70. 70.
    Pawelec G, Wernet P, Rehbein A, Balko I, Schneider EM (1984) Alloproliferative human T cell clones primed and cultured in vitro lose proliferative and gain suppressive activity with age. Hum Immunol 10:135–144PubMedCrossRefGoogle Scholar
  71. 71.
    von Boehmer H, Kisielow P, Leisseron W, Haas W (1984) Lyt2 T cell-independent function of Lyt 2+ cells stimulated with antigen of Concanavalin A. J Immunol 133:59–64Google Scholar
  72. 72.
    Wee S-L, Ochoa AC, Bach FH (1985) Human alloreactive CTL clones: loss and reac-quisition of specific cytolytic activity can be regulated by “recombinant” interleukin 2. J Immunol 134:310–313PubMedGoogle Scholar
  73. 73.
    Fleischer B (1984) Acquisition of specific cytotoxic activity by human T4+ lymphocytes in culture. Nature 308:365–367PubMedCrossRefGoogle Scholar
  74. 74.
    Claesson MH, Miller RG (1985) Functional heterogeneity in allospecific cytotoxic T lymphocyte clones. II. Development of syngeneic cytotoxicity in the absence of specific antigenic stimulation. J Immunol 134:684–690PubMedGoogle Scholar
  75. 75.
    Simon MM, Weltzien H-U, Bühring H-J, Eichmann K (1984) Aged murine killer T cell clones acquire specific cytotoxicity for P815 mastocytoma cells. Nature 308:367–370PubMedCrossRefGoogle Scholar
  76. 76.
    Acha-Orbea H, Groscurth P, Lang R, Stitz L, Hengartner H (1983) Characterization of cloned cytotoxic lymphocytes with NK-like activity. J Immunol 130:2952–2959PubMedGoogle Scholar
  77. 77.
    Binz H, Fenner M, Frei D, Wigzell H (1983) Two independent receptors allow selective target cell lysis by T cell clones. J Exp Med 157:1252–1260PubMedCrossRefGoogle Scholar
  78. 78.
    Brooks CG (1983) Reversible induction of natural killer cell activity in cloned murine cytotoxic lymphocytes. Nature 305:155–158PubMedCrossRefGoogle Scholar
  79. 79.
    Augustin A A, Sim GK (1984) T cell receptors generated via mutations are specific for various histocompatibility antigens. Cell 39:5–12PubMedCrossRefGoogle Scholar
  80. 80.
    Falcioni F, Pawelec G, Brattig N, Schneider EM, Berg P, Wernet P (1985) Regulation of lymphoproliferation and Ig secretion by lymphocyte clones in man. Immunology 54:685–692PubMedGoogle Scholar
  81. 81.
    Pawelec G, Busch FW, Schneider EM, Rehbein A, Balko I, Wernet P (1985) Acquisition of suppressive and natural killer-like activities associated with loss of alloreactivity in human “helper” T clones. Curr Top Microbiol Immunol (in press)Google Scholar
  82. 82.
    Schneider EM, Pawelec G, Shi LR, Wernet P (1984) A novel type of human T cell clone with highly potent natural killer-like cytotoxicity divorced from large granular lymphocyte morphology. J Immunol 133:173–179PubMedGoogle Scholar
  83. 83.
    Lamb JR, Skidmore BJ, Green N, Chiller JM, Feldmann M (1983) Induction of tolerance in influenza virus-immune T lymphocyte clones with synthetic peptides of influenza hemagglutinin. J Exp Med 157:1434–1447PubMedCrossRefGoogle Scholar
  84. 84.
    Feldmann M, Zanders ED, Lamb JR (1985) Tolerance in T cell clones. Immunol Today 6:58–62CrossRefGoogle Scholar
  85. 85.
    Zanders ED, Lamb JR, Feldmann M, Green N, Beverley PCL (1983) Tolerance of T cell clones is associated with membrane antigen changes. Nature 303:625–627PubMedCrossRefGoogle Scholar
  86. 86.
    Reinherz EL, Meuer SC, Schlossman SF (1983) The human T cell receptor: analysis with cytotoxic T cell clones. Immunol Rev 74:83–112PubMedCrossRefGoogle Scholar
  87. 87.
    Moretta A, Pantaleo G, Mingari MC, Moretta L, Cerottini J-C (1984) Clonal heterogeneity in the requirement for T3, T4, and T8 molecules in human cytolytic T lymphocyte function. J Exp Med 159:921–934PubMedCrossRefGoogle Scholar
  88. 88.
    Spits H, Yssel H, Leeuwenberg J, de Vries JE (1985) Antigen-specific cytotoxic T cell and antigen-specific proliferating T cell clones can be induced to cytolytic activity by monoclonal antibodies against T3. Eur J Immunol 15:88–91PubMedCrossRefGoogle Scholar
  89. 89.
    Wilde DB, Fitch FW (1984) Antigen-reactive cloned helper T cells. I. Unresponsiveness to antigen restimulation develops after stimulation of cloned helper T cells. J Immunol 132:1632–1638PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1986

Authors and Affiliations

  • P. Wernet
  • G. Pawelec
  • E. M. Schneider

There are no affiliations available

Personalised recommendations