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. 1986 Feb;83(3):762–766. doi: 10.1073/pnas.83.3.762

Human T-cell clones used to define functional epitopes on HLA class II molecules.

C M Weyand, J Goronzy, C G Fathman
PMCID: PMC322945  PMID: 2418442

Abstract

Polyclonal reagents have been used to define HLA class II molecules in conventional serologic and cellular typing. We generated human alloreactive T-cell clones to analyze the functional fine specificities of HLA class II molecules that might be important for the phenomenon of HLA and disease association. We chose to examine HLA-Dw14, an HLA-D specificity that has been associated with juvenile rheumatoid arthritis. In this paper we have presented data that suggest that conventional cellular typing does not reflect the distribution of T-cell epitopes on major histocompatibility complex class II molecules. We describe three alloreactive T-cell clones that have defined three separate Dw14-associated T-cell epitopes. Two of these epitopes were on a DR-region molecule; the third was located on a DQ-region product. In a panel of unrelated DR4-positive donors, these three DW14-associated determinants were present in a high frequency but were not linked to each other. Within the tested panel of DR4-positive cells, all possible combinatorial arrangements of these three allodeterminants were seen. The concurrent expression of any two of the three allodeterminants was equivalent to a positive typing response for Dw14. Our finding that HLA-Dw14 is not characterized by a unique allodeterminant but by the combinatorial recognition of independently distributed T-cell interaction sites suggests that analysis of HLA and disease association may be more clearly demonstrated through the use of human T-cell clones.

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Selected References

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

  1. Austin P., Trowsdale J., Rudd C., Bodmer W., Feldmann M., Lamb J. Functional expression of HLA-DP genes transfected into mouse fibroblasts. Nature. 1985 Jan 3;313(5997):61–64. doi: 10.1038/313061a0. [DOI] [PubMed] [Google Scholar]
  2. Chen Y. X., Evans R. L., Pollack M. S., Lanier L. L., Phillips J. H., Rousso C., Warner N. L., Brodsky F. M. Characterization and expression of the HLA-DC antigens defined by anti-Leu 10. Hum Immunol. 1984 Aug;10(4):221–235. doi: 10.1016/0198-8859(84)90088-0. [DOI] [PubMed] [Google Scholar]
  3. Dupont B., Jersild C., Hansen G. S., Nielsen L. S., Thomsen M., Svejgaard A. Typing for MLC determinants by means of LD-homozygous and LD-heterozygous test cells. Transplant Proc. 1973 Dec;5(4):1543–1549. [PubMed] [Google Scholar]
  4. Fathman C. G., Hengartner H. Crossreactive mixed lymphocyte reaction determinants recognized by cloned alloreactive T cells. Proc Natl Acad Sci U S A. 1979 Nov;76(11):5863–5866. doi: 10.1073/pnas.76.11.5863. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Finn O. J., Levy R. Multiple HLA-DR antigens: detection with monoclonal antibodies and translation in vitro. Proc Natl Acad Sci U S A. 1982 Apr;79(8):2658–2662. doi: 10.1073/pnas.79.8.2658. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Giles R. C., Nunez G., Hurley C. K., Nunez-Roldan A., Winchester R., Stastny P., Capra J. D. Structural analysis of a human I-A homologue using a monoclonal antibody that recognizes an MB3-like specificity. J Exp Med. 1983 May 1;157(5):1461–1470. doi: 10.1084/jem.157.5.1461. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Groner J. P., Watson A. J., Bach F. H. Dw/LD-related molecular polymorphism of DR4 beta-chains. J Exp Med. 1983 May 1;157(5):1687–1691. doi: 10.1084/jem.157.5.1687. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Hsu S. H., Chan M. M., Bias W. B. Genetic control of major histocompatibility complex-linked immune responses to synthetic polypeptides in man. Proc Natl Acad Sci U S A. 1981 Jan;78(1):440–444. doi: 10.1073/pnas.78.1.440. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. 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]
  10. Morling N., Platz P., Ryder L. P., Svejgaard A., Thomsen M. Data reduction in HLA-D typing with the primed lymphocyte typing (PLT) technique. the normalized median response (NMR). Tissue Antigens. 1980 Feb;15(2):123–136. doi: 10.1111/j.1399-0039.1980.tb00897.x. [DOI] [PubMed] [Google Scholar]
  11. Morling N., Platz P., Ryder L. P., Svejgaard A., Thomsen M. Generation of HLA-D specific primed lymphocyte typing (PLT) cells and cross-reactions of PLT-cells primed with homozygous typing cells. Tissue Antigens. 1980 Feb;15(2):137–151. doi: 10.1111/j.1399-0039.1980.tb00898.x. [DOI] [PubMed] [Google Scholar]
  12. Nepom B. S., Nepom G. T., Mickelson E., Antonelli P., Hansen J. A. Electrophoretic analysis of human HLA-DR antigens from HLA-DR4 homozygous cell lines: correlation between beta-chain diversity and HLA-D. Proc Natl Acad Sci U S A. 1983 Nov;80(22):6962–6966. doi: 10.1073/pnas.80.22.6962. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Nepom B. S., Nepom G. T., Mickelson E., Schaller J. G., Antonelli P., Hansen J. A. Specific HLA-DR4-associated histocompatibility molecules characterize patients with seropositive juvenile rheumatoid arthritis. J Clin Invest. 1984 Jul;74(1):287–291. doi: 10.1172/JCI111413. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Nepom G. T., Nepom B. S., Antonelli P., Mickelson E., Silver J., Goyert S. M., Hansen J. A. The HLA-DR4 family of haplotypes consists of series of distinct DR and DS molecules. J Exp Med. 1984 Feb 1;159(2):394–404. doi: 10.1084/jem.159.2.394. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Reinsmoen N. L., Bach F. H. Five HLA-D clusters associated with HLA-DR4. Hum Immunol. 1982 Jun;4(3):249–258. doi: 10.1016/0198-8859(82)90040-4. [DOI] [PubMed] [Google Scholar]
  16. Sasazuki T., Kohno Y., Iwamoto I., Tanimura M., Naito S. Association between an HLA haplotype and low responsiveness to tetanus toxoid in man. Nature. 1978 Mar 23;272(5651):359–361. doi: 10.1038/272359b0. [DOI] [PubMed] [Google Scholar]
  17. Sasazuki T., McDevitt H. O., Grumet F. C. The association between genes in the major histocompatibility complex and disease susceptibility,. Annu Rev Med. 1977;28:425–452. doi: 10.1146/annurev.me.28.020177.002233. [DOI] [PubMed] [Google Scholar]
  18. Schwartz R. H., Fathman C. G., Sachs D. H. Inhibition of stimulation in murine mixed lymphocyte cultures with an alloantiserum directed against a shared Ia determinant. J Immunol. 1976 Apr;116(4):929–935. [PubMed] [Google Scholar]
  19. Segall M., Reinsmoen N. L., Iwaki J., Bach F. H. Determinants not correlated with HLA-Dw, DR, or SB detected by primed lymphocyte typing. Hum Immunol. 1982 Jun;4(3):239–248. doi: 10.1016/0198-8859(82)90039-8. [DOI] [PubMed] [Google Scholar]
  20. Svejgaard A., Platz P., Ryder L. P. HLA and disease 1982--a survey. Immunol Rev. 1983;70:193–218. doi: 10.1111/j.1600-065x.1983.tb00715.x. [DOI] [PubMed] [Google Scholar]
  21. Watson A. J., DeMars R., Trowbridge I. S., Bach F. H. Detection of a novel human class II HLA antigen. 1983 Jul 28-Aug 3Nature. 304(5924):358–361. doi: 10.1038/304358a0. [DOI] [PubMed] [Google Scholar]

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