title: Allele-specific control of Ia molecule surface expression and conformation: implications for a general model of Ia structure-function relationships.
abstract: Sequence polymorphism of class II major histocompatibility complex-encoded molecules (Ia) not only accounts for the allelic variability in Ia structure relevant to T-lymphocyte responses but also seems to result in differential quantitative expression of particular Ia heterodimers. The contributions of different allelically variable regions of Ia molecules to both of these processes were analyzed by transfection of L cells with various A beta and A alpha gene pairs. The results show that, with regard to quantitative and qualitative aspects of Ia expression, the polymorphisms in the A beta chain segregate into two groups. Those in the NH2-terminal half of A beta 1 have a consistent role in controlling beta-alpha chain interactions, efficiency of dimer expression, and Ia conformation and probably are in the interior of the Ia molecule at the site of beta-alpha domain interaction. Polymorphisms in the COOH-terminal half of A beta 1 contribute to those structures that directly interact with antibodies, antigen, and/or T-cell receptors, consistent with their presence on the surface of the Ia heterodimer. This analysis provides a model for understanding both overall class II molecular structure and the relationship between this structure and immune recognition. It also suggests an explanation for the evolution of certain features of class II genes.
mesh_terms: D000483:Alleles; D000818:Animals; D002462:Cell Membrane / Q000276:immunology; D004247:DNA / Q000378:metabolism; D004262:DNA Restriction Enzymes; D005796:Genes; D005802:Genes, MHC Class II; D000949:Histocompatibility Antigens Class II / Q000032:analysis / Q000276:immunology*; D007739:L Cells / Q000276:immunology; D051379:Mice; D008957:Models, Genetic
chemical_list: D000949:Histocompatibility Antigens Class II; D004247:DNA; D004262:DNA Restriction Enzymes