T cell responses specific for subregions of allogeneic MHC molecules.
The repertoire of C3H (H-2k) CD4+ T cells for I-Ab allopolymorphisms was analyzed by studying the responses of unprimed populations of T cells and of I-Ab-specific T cell clones for recombinant MHC molecules containing combinations of polymorphic subregions of the alpha- and beta-chains from the I-Ab and I-Ak molecules. In this system, polymorphisms in the predicted MHC alpha-helices were more potent than polymorphisms in the beta-strands in stimulating unprimed alloreactive T cells. Similarly, 75% of I-Ab-specific T cell clones responded to recombinants containing b polymorphisms in both the alpha- and beta-chains helices and tolerated the substitution of k polymorphisms in the beta-pleated sheet. Furthermore, 20% of the clones responded to a molecule containing allogeneic b residues in just the beta-chain helix. The results demonstrate that the T cell response to allogeneic MHC molecules consists largely of sets of T cells with overlapping specificities for subregions of the MHC molecule. In addition, they highlight the importance of the alpha-helices in these responses and a diminished role for polymorphisms in the beta-strands when, as in the present case, MHC structure and conformation is tolerant of beta-sheet substitutions. These results sharply contrast with observations made in the analysis of Ag-specific T cells and lead to the suggestion that a subset of alloreactive T cells are not peptide specific and can directly recognize MHC polymorphisms.
Berkowitz
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Department of Medicine, Columbia University, College of Physicians and Surgeons, New York, NY 10032.
Braunstein
N S
NS
D000818:Animals; D002999:Clone Cells; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D007739:L Cells; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D011110:Polymorphism, Genetic; D011487:Protein Conformation; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D011994:Recombinant Proteins / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D014162:Transfection
D000949:Histocompatibility Antigens Class II; D011948:Receptors, Antigen, T-Cell; D011994:Recombinant Proteins