Immune response gene function correlates with the expression of an Ia antigen. I. Preferential association of certain Ae and E alpha chains results in a quantitative deficiency in expression of an Ae:E alpha complex.

ABSTRACT

These studies were stimulated by the observation, reported in the accompanying paper (19), that IEu failed to interact with I-Ak or I-As in F1 mice to allow a response to the antigen, pigeon cytochrome c, unlike I-E subregions derived from other Ia.7+ haplotypes. Serological and biochemical analyses were performed to determine whether or not cells from these F1 mice express the Ak,seE alpha complexes that should function as restriction elements for T cell recognition of pigeon cytochrome c on antigen-presenting cells. Using the Y-17 monoclonal antibody, which recognizes the combinatorial or conformational determinant Ia.m44 on certain AeE alpha complexes, we were able to distinguish between AueEu alpha and Ab,k,seEu alpha complexes on cell surfaces. Although complement-dependent microcytotoxicity with Y-17 failed to detect Ab,k,seEu alpha complexes on cells from appropriate F1 mice, these molecules were detected by both quantitative absorption and quantitative immunofluorescence studies. However, Ab,k,seEu alpha complexes were found to be present at levels only one-seventh to one-eighth the levels expressed by homozygous I-Ab, I-Ek; I-Ak, I-Ek; and I-As, I-Ek cells. The results of two-dimensional polyacrylamide gel electrophoresis analyses suggest that the low levels of expression of Ab,k,seEu alpha complexes are a consequence of the preferential association of Aue and Eu alpha chains with each other in the F1 cells. As will be shown in the following paper (19), the quantitative deficiency in the expression of AkeEu alpha and AseEu alpha complexes results in a corresponding defect in antigen-presenting cell function, thus providing strong evidence that Ia antigens represent products of Ir genes.