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. 1980 Sep 1;152(3):565–580. doi: 10.1084/jem.152.3.565

Evidence for a new segregant series of B cell antigens that are encoded in the HLA-D region and that stimulate secondary allogenic proliferative and cytotoxic responses

PMCID: PMC2185933  PMID: 6967946

Abstract

Five new histocompatibility antigens, designated secondary B cell or (SB) antigens, have been identified by secondary allogeneic proliferative and cytotoxic responses. The reagents used to define the SB antigents are lymphocytes primed between donors matched for all known HLA antigens. The SB antigens stimulate weak primary allogeneic proliferative responses (a mean relative response of 8%) but strong secondary proliferative responses. Strong secondary cell-mediated cytotoxicity is generated against target antigens that are distinguishable from the SB antigens defined by proliferation. Studies by direct lysis and by cold-target inhibition indicate that these target antigens are preferentially expressed on B cells relative to T cells. The SB antigens segregate with HLA, and the gene(s) encoding the SB1, 3, and 4 antigens maps centromeric to HLA-B. The SB antigens are major histocompatibility antigens not only because they are encoded by major histocompatibility complex (MHC) genes, but also by the functional criteria that the proliferative and cytotoxic responses to SB antigens are not restricted by HLA-DR or HLA-A,-B. Parallel studies of the SB antigens and the DR antigens with respect to: (a) their preferential expression on B cells, (b) their function in secondary allogeneic proliferative and cytotoxic respones, and (c) the location of their structural gene within the MHC. However, the SB antigens and the DR antigens are clearly distinct antigens, because population studies indicate that they can occur independently, and family studies indicate that specific SB antigens segregate with HLA haplotypes having different D and DR specificities. Our data are consistent with the hypotheses that the SB antigens are a new segregant series of B cell alloantigens, and that the SB gene and the DR gene derive from a duplicated ancestral gene.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Albrechtsen D., Arnesen E., Thorsby E. Cell-mediated lymphocytotoxicity directed against HLA-D gene products. Transplantation. 1979 May;27(5):338–341. doi: 10.1097/00007890-197905000-00010. [DOI] [PubMed] [Google Scholar]
  2. Bergholtz B. O., Thorsby E. Macrophage-dependent response of immune human T lymphocytes to PPD in vitro. Influence of HLA-D histocompatibility. Scand J Immunol. 1977;6(8):779–786. doi: 10.1111/j.1365-3083.1977.tb02151.x. [DOI] [PubMed] [Google Scholar]
  3. Biddison W. E., Payne S. M., Shearer G. M., Shaw S. Human cytotoxic T cell responses to trinitrophenyl hapten and influenza virus. Diversity of restriction antigens and specificity of HLA-linked genetic regulation. J Exp Med. 1980 Aug 1;152(2 Pt 2):204s–217s. [PubMed] [Google Scholar]
  4. Bodmer W. F., Bodmer J. G. Evolution and function of the HLA system. Br Med Bull. 1978 Sep;34(3):309–316. doi: 10.1093/oxfordjournals.bmb.a071518. [DOI] [PubMed] [Google Scholar]
  5. Charron D. J., McDevitt H. O. Analysis of HLA-D region-associated molecules with monoclonal antibody. Proc Natl Acad Sci U S A. 1979 Dec;76(12):6567–6571. doi: 10.1073/pnas.76.12.6567. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Doherty P. C., Zinkernagel R. M. A biological role for the major histocompatibility antigens. Lancet. 1975 Jun 28;1(7922):1406–1409. doi: 10.1016/s0140-6736(75)92610-0. [DOI] [PubMed] [Google Scholar]
  7. Duquesnoy R. J., Marrari M., Annen K. Identification of an HLA-DR-associated system of B-cell alloantigens. Transplant Proc. 1979 Dec;11(4):1757–1760. [PubMed] [Google Scholar]
  8. Feighery C., Stastny P. HLA-D region-associated determinants serve as targets for human cell-mediated lysis. J Exp Med. 1979 Feb 1;149(2):485–494. doi: 10.1084/jem.149.2.485. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Fradelizi D., Dausset J. Mixed lymphocyte reactivity of human lymphocytes primed in vitro. I. Secondary response to allogenic lymphocytes. Eur J Immunol. 1975 May;5(5):295–301. doi: 10.1002/eji.1830050502. [DOI] [PubMed] [Google Scholar]
  10. Hartzman R. J., Pappas F., Romano P. J., Johnson A. H., Ward F. E., Amos D. B. Dissociation of HLA-D and HLA-DR using primed LD typing. Transplant Proc. 1978 Dec;10(4):809–812. [PubMed] [Google Scholar]
  11. Johnsen H. E. Human B-blast specific target determinants in CML: a panel study. Tissue Antigens. 1980 Feb;15(2):199–209. doi: 10.1111/j.1399-0039.1980.tb00904.x. [DOI] [PubMed] [Google Scholar]
  12. Klein J. The major histocompatibility complex of the mouse. Science. 1979 Feb 9;203(4380):516–521. doi: 10.1126/science.104386. [DOI] [PubMed] [Google Scholar]
  13. Ko H. S., Fu S. M., Winchester R. J., Yu D. T., Kunkel H. G. Ia determinants on stimulated human T lymphocytes. Occurrence on mitogen- and antigen-activated T cells. J Exp Med. 1979 Aug 1;150(2):246–255. doi: 10.1084/jem.150.2.246. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kristensen T. Studies on the specificity of CML. Report from a CML-workshop. Tissue Antigens. 1978 Apr;11(4):330–349. doi: 10.1111/j.1399-0039.1978.tb01266.x. [DOI] [PubMed] [Google Scholar]
  15. Lampson L. A., Levy R. Two populations of Ia-like molecules on a human B cell line. J Immunol. 1980 Jul;125(1):293–299. [PubMed] [Google Scholar]
  16. Seldin M. F., Rich R. R. Human immune responses to hapten-conjugated cells. I. Primary and secondary proliferative responses in vitro. J Exp Med. 1978 Jun 1;147(6):1671–1683. doi: 10.1084/jem.147.6.1671. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Shackelford D. A., Strominger J. L. Demonstration of structural polymorphism among HLA-DR light chains by two-dimensional gel electrophoresis. J Exp Med. 1980 Jan 1;151(1):144–165. doi: 10.1084/jem.151.1.144. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Shaw S., Nelson D. L., Shearer G. M. Human cytotoxic response in vitro to trinitrophenyl-modified autologous cells. I. T cell recognition of TNP in association with widely shared antigens. J Immunol. 1978 Jul;121(1):281–289. [PubMed] [Google Scholar]
  19. Shaw S., O'Neill G. J., Shearer G. M. Immunogenetic analysis of an unusual HLA region recombination by intrafamilial MLR, PLT, and CMC. Transplant Proc. 1979 Dec;11(4):1804–1808. [PubMed] [Google Scholar]
  20. Shaw S., Shearer G. M., Biddison W. E. Human cytotoxic T-cell responses to type A and type B influenza viruses can be restricted by different HLA antigens. Implications for HLA polymorphism and genetic regulation. J Exp Med. 1980 Jan 1;151(1):235–245. doi: 10.1084/jem.151.1.235. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Sheehy M. J., Sondel P. M., Bach M. L., Wank R., Bach F. H. HL-A LD (lymphocyte defined) typing: a rapid assay with primed lymphocytes. Science. 1975 Jun 27;188(4195):1308–1310. doi: 10.1126/science.124948. [DOI] [PubMed] [Google Scholar]
  22. Thorley-Lawson D. A., Chess L., Strominger J. L. Suppression of in vitro Epstein-Barr virus infection. A new role for adult human T lymphocytes. J Exp Med. 1977 Aug 1;146(2):495–508. doi: 10.1084/jem.146.2.495. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Tosi R., Tanigaki N., Centis D., Ferrara G. B., Pressman D. Immunological dissection of human Ia molecules. J Exp Med. 1978 Dec 1;148(6):1592–1611. doi: 10.1084/jem.148.6.1592. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Wank R., Schendel D. J., Blanco M. E., Dupont B. Secondary MLC responses of primed lymphocytes after selective sensitization to non-HLA-D determinants. Scand J Immunol. 1979;9(6):499–505. doi: 10.1111/j.1365-3083.1979.tb03277.x. [DOI] [PubMed] [Google Scholar]

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