Abstract
An in vitro model was developed to study both primary and secondary proliferative responses of human lymphocytes to hapten-conjugated peripheral blood mononuclear cells. Coculture of human lymphocytes with autologous trinitrophenyl (TNP)-conjugated stimulator cells resulted in primary proliferative responses. Subjects segregated into high and low primary responders with mean stimulation indices of 11 and 2.1, respectively. Restimulation of primed cells from high responder subjects 3 wk after initial sensitization generated secondary proliferative responses. To investigate the antigenic requirements for secondary stimulation, autologous TNP-conjugate primed responders were restimulated with both autologous and allogeneic TNP-conjugated stimulators. In all experiments restimulation with autologous conjugated cells yielded substantially greater proliferative responses than with allogeneic conjugates. Experiments were then performed to ascertain whether HLA determinant homology between primed responder and stimulator cells influenced the level of secondary responsiveness. Homology for HLA-A and B locus serologic determinants was not associated with enhanced responsiveness. In contrast, D region determinant homology, detected by B-cell antigen typing, showed a highly significant positive correlation with the magnitude of secondary responses. The data thus strongly suggest that for secondary proliferative responses to TNP, human T cells recognize hapten in association with HLA-D region determinants.
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- Albert E. D., Mempel W., Grosse-Wilde H. Linkage disequilibrium between HL-A7 and the MLC specificity Pi. Transplant Proc. 1973 Dec;5(4):1551–1553. [PubMed] [Google Scholar]
- Bach F. H., van Rood J. J. The major histocompatibility complex - genetics and biology (third of three parts). N Engl J Med. 1976 Oct 21;295(17):927–936. doi: 10.1056/NEJM197610212951705. [DOI] [PubMed] [Google Scholar]
- Barbosa J., King R., Noreen H., Yunis E. J. The histocompatibility system in juvenile, insulin-dependent diabetic multiplex kindreds. J Clin Invest. 1977 Nov;60(5):989–998. doi: 10.1172/JCI108879. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bevan M. J. The major histocompatibility complex determines susceptibility to cytotoxic T cells directed against minor histocompatibility antigens. J Exp Med. 1975 Dec 1;142(6):1349–1364. doi: 10.1084/jem.142.6.1349. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Blumenthal M. N., Amos D. B., Noreen H. Genetic mapping of Ir locus in man: linkage to second locus of HL-A. Science. 1974 Jun 21;184(4143):1301–1303. doi: 10.1126/science.184.4143.1301. [DOI] [PubMed] [Google Scholar]
- Böyum A. Isolation of mononuclear cells and granulocytes from human blood. Isolation of monuclear cells by one centrifugation, and of granulocytes by combining centrifugation and sedimentation at 1 g. Scand J Clin Lab Invest Suppl. 1968;97:77–89. [PubMed] [Google Scholar]
- Dickmeiss E., Soeberg B., Svejgaard A. Human cell-mediated cytotoxicity against modified target cells is restricted by HLA. Nature. 1977 Dec 8;270(5637):526–528. doi: 10.1038/270526a0. [DOI] [PubMed] [Google Scholar]
- Doherty P. C., Blanden R. V., Zinkernagel R. M. Specificity of virus-immune effector T cells for H-2K or H-2D compatible interactions: implications for H-antigen diversity. Transplant Rev. 1976;29:89–124. doi: 10.1111/j.1600-065x.1976.tb00198.x. [DOI] [PubMed] [Google Scholar]
- Levis W. R., Dattner A. M. Clonal priming of lymphocytes can measure human immune-response gene function. N Engl J Med. 1977 Oct 13;297(15):842–843. doi: 10.1056/NEJM197710132971521. [DOI] [PubMed] [Google Scholar]
- McDevitt H. O., Benacerraf B. Genetic control of specific immune responses. Adv Immunol. 1969;11:31–74. doi: 10.1016/s0065-2776(08)60477-0. [DOI] [PubMed] [Google Scholar]
- McDevitt H. O., Oldstone B. A., Pincus T. Histocompatibility-linked genetic control of specific immune responses to viral infection. Transplant Rev. 1974;19(0):209–225. doi: 10.1111/j.1600-065x.1974.tb00133.x. [DOI] [PubMed] [Google Scholar]
- Newman W., Stoner G. L., Bloom B. R. Primary in vitro sensitisation of human T cells. Nature. 1977 Sep 8;269(5624):151–153. doi: 10.1038/269151a0. [DOI] [PubMed] [Google Scholar]
- Rich S. S., Rich R. R. Regulatory mechanisms in cell-mediated immune responses. I. Regulation of mixed lymphocyte reactions by alloantigen-activated thymus-derived lymphocytes. J Exp Med. 1974 Dec 1;140(6):1588–1603. doi: 10.1084/jem.140.6.1588. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rubinstein P., Suciu-Foca N., Nicholson J. F. Genetics of juvenile diabetes mellitus. A recessive gene closely linked to HLA D and with 50 per cent penetrance. N Engl J Med. 1977 Nov 10;297(19):1036–1040. doi: 10.1056/NEJM197711102971905. [DOI] [PubMed] [Google Scholar]
- Schmitt-Verhulst A. M., Garbarino C. A., Shearer G. M. H-2 homology requirements for secondary cell-mediated lympholysis and miced lymphocyte reactions to TNP-modified syngeneic lymphocytes. J Immunol. 1977 Apr;118(4):1420–1427. [PubMed] [Google Scholar]
- Shearer G. M. Cell-mediated cytotoxicity to trinitrophenyl-modified syngeneic lymphocytes. Eur J Immunol. 1974 Aug;4(8):527–533. doi: 10.1002/eji.1830040802. [DOI] [PubMed] [Google Scholar]
- Shearer G. M., Rehn T. G., Schmitt-Verhulst A. M. Role of the murine major histocompatibility complex in the specificity of in vitro T-cell-mediated lympholysis against chemically-modified autologous lymphocytes. Transplant Rev. 1976;29:222–246. doi: 10.1111/j.1600-065x.1976.tb00203.x. [DOI] [PubMed] [Google Scholar]
- Sondel P. M., Jacobson M. W., Bach F. H. Pre-emption of human cell-mediated lympholysis by a suppressive mechanism activated in mixed lymphocyte cultures. J Exp Med. 1975 Dec 1;142(6):1606–1611. doi: 10.1084/jem.142.6.1606. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Svejgaard A., Platz P., Ryder L. P., Nielsen L. S., Thomsen M. HL-A and disease associations--a survey. Transplant Rev. 1975;22:3–43. doi: 10.1111/j.1600-065x.1975.tb01550.x. [DOI] [PubMed] [Google Scholar]
- Ting A., Mickey M. R., Terasaki P. I. B-lymphocyte alloantigens in Caucasians. J Exp Med. 1976 Apr 1;143(4):981–986. doi: 10.1084/jem.143.4.981. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yano A., Schwartz R. H., Paul W. E. Antigen presentation in the murine T-lymphocyte proliferative response. I. Requirement for genetic identity at the major histocompatibility complex. J Exp Med. 1977 Sep 1;146(3):828–843. doi: 10.1084/jem.146.3.828. [DOI] [PMC free article] [PubMed] [Google Scholar]