Previous studies on negative selection of T cells to sheep erythrocytes in irradiated mice showed that CBA (I-Ak,I-Ek) (kk) T cells comprise two subgroups of cells restricted by I-A (A alpha-A beta) and I-A/E (E alpha-E beta) molecules. Selection of the I-A/E-restricted by I-A (A alpha-A beta) and I-A/E (E alpha-E beta) molecules. Selection of the I-A/E-restricted subset requires that the donor T cells and the selection host share both I-A (E beta) and I-E (E alpha) gene products; only the I-A-restricted cells undergo selection in B10.A(4R) (kb) mice. This paper demonstrates that negative selection of the I-A/E-restricted subgroup of CBA T cells can occur in F1 hybrids between B10.A(4R) and various Ia.7+ (E alpha+) I-E-incompatible strains; selection does not occur in hybrids between B10.A(4R) and Ia.7- (E alpha-) strains. These data suggest that, despite the fact that E alpha chains display detectable structural allelic variations, these chains are functionally nonpolymorphic. This conclusion applies to E alpha k,d,p,r,j chains. With F1 hybrids between B10.A(4R) and another Ia.7+ strain, B10.PL (H-2u), in contrast, only intermediate selection is observed. This finding is consistent with recent evidence that cell surface expression of E alpha-u-E beta dimers displays strong cis preference. In contrast to E alpha+ CBA T cells, E alpha- B10.A(4R) (kb) T cells undergo complete negative selection in hosts matched only in the I-A (and H-2K) subregion, i.e., B10.BR (kk) mice; no selection occurs in B10 (bb) mice. These data imply that Ia-restricted T cells in E alpha- strains are probably restricted solely by I-A molecules.

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