Genetic control of T-cell proliferative responses to poly(glu40ala60) and poly(glu51lys34tyr15): subregion-specific inhibition of the responses with monoclonal Ia antibodies.
The relationship between Ir genes and Ia antigens was studied in the T-cell proliferative responses to two synthetic polypeptides poly(glu40ala60) (GA) and poly(glu51lys34tyr15) (GLT15). The response to GA was found to be controlled by an Ir gene in the I-A subregion, whereas the anti-GLT15 response was shown to be under dual control, one Ir gene mapping probably in the I-A subregion, and the other in the I-E subregion. We obtained two different lines of evidence suggesting identity of Ir and Ia genes. First, the presence of certain serologically identified allelic forms of the I-A-encoded A molecule correlated with the responder status to GA both in inbred strains and in B10.W lines, the latter carrying wild-derived H-2 haplotypes. Thus the Ir and Ia phenotypes were not separable in strains of independent origin. Second, the anti-GA response was completely inhibited by monoclonal antibodies against determinants on the A molecule (Ia.8, 15, and 19), but not by a monoclonal antibody against a determinant on the E molecule (Ia.7). In contrast, the anti-GLT15 response was only inhibited by a monoclonal antibody against the E molecule, but not by antibodies against the A molecule. Our data support the hypothesis that Ia antigens, as restriction elements for T-cell recognition, may in fact be the phenotypic manifestation of Ir genes.
D000409:Alanine / Q000031:analogs & derivatives / Q000276:immunology; D000818:Animals; D005260:Female; D005802:Genes, MHC Class II; D000949:Histocompatibility Antigens Class II / Q000235:genetics*; D008213:Lymphocyte Activation / Q000235:genetics; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010455:Peptides / Q000276:immunology*; D011099:Polyglutamic Acid / Q000276:immunology; D011108:Polymers; D013601:T-Lymphocytes / Q000276:immunology
D000949:Histocompatibility Antigens Class II; D010455:Peptides; D011108:Polymers; D011099:Polyglutamic Acid; C022272:glutamic acid-lysine-tyrosine terpolymer; C036437:poly(glutamic acid-alanine); D000409:Alanine