Differential expression of Ia glycoprotein complexes in F1 hybrid mice detected with alloreactive cloned T cell lines.

T cell lines alloreactive to Aeb:E alpha Ia antigen complexes have been prepared and used to determine the relative amount of Aeb:E alpha expressed by stimulator cells in homozygous recombinant and F1 mice expressing these complexes. We find that homozygous cells stimulate most strongly and therefore probably express the highest density of Aeb:E alpha. Among heterozygotes, H-2bxd F1 mice preferentially express Aeb:E alpha d complexes, H-2bxa F1 mice express relatively fewer Aeb:E alpha k complexes, and H-2bxu F1 mice express preferentially Aeu:E alpha u complexes. This differential association of Aeb chains with E alpha chains thus influences the biologic activity of these Ia antigens in this and other functional assays. The functional data are supported by biochemical analysis of Aeb:E alpha complex expression. These findings suggest that a reanalysis of HLA-DR associations with human diseases should be undertaken in which both HLA-DR alleles are included, with the prediction that certain combinations would show greater susceptibility, whereas others would show less susceptibility than predicted from the susceptibility associated with presence of a single allele at HLA-DR.