Gene complementation in the T lymphocyte proliferative response to poly (Glu56Lys35Phe9)n. Functional evidence for a restriction element coded for by both the I-A and I-E subregions.

Abstract

AbstractThe T lymphocyte proliferative response to poly(Glu56Lys35Phe9)n (GLΦ) is under the control of two immune response genes, Ir‐GLΦ‐β and Ir‐GLΦ‐α, mapping in the I‐A and I‐E/C subregions of the major histocompatibility complex, respectively. Previous studies have demonstrated that in order to generate a response to GLΦ, both gene products must be expressed in the antigen‐presenting cell (APC) but that neither responder allele has to be present in the responding T lymphocyte, provided that the T cell has matured in a responder environment. These results suggested that both gene products function as restricting elements in GLΦ presentation by APC. In this report, we provide further evidence for this model from experiments designed to test histocompatibility restrictions in antigen presentation at the I‐E/C subregion. Genetic identity at the I‐A subregion between T cells and APC was required for GLΦ presentation. To assess the requirements at I‐E/C, B10. A(5R) T cells (I‐Ab, I‐Ek) primed to GLΦ were stimulated in vitro with GLΦ‐pulsed spleen cells from F1 hybrids between C57BL/10 (B10: I‐Ab, I‐Eb) which made the cells compatible at I‐A, and a variety of B10 congenics bearing other H‐2 haplotypes. Although none of the parental spleen cells could present GLΦ to B10.A(5R) T cells, spleen cells from F1 hybrids between B10 and strains possessing H‐2I of k, d, p and r presented GLΦ, whereas hybrids with strains possessing H‐2I of f, q and s failed to present. This pattern of complementation for GLΦ presentation could not be explained on the basis of the responder status of the I‐E/C donating parental haplotypes nor by invoking inhibitory stimuli from mixed lymphocyte reactions induced by the Fl APC. Rather, the pattern correlated with the presence of the serologic marker Ia.7 coded for by the I‐E subregion of the complementing parental haplotype and the possession of an I‐E‐encoded a chain which has been shown by peptide mapping to be very similar in strains bearing the k, d, p and r haplotypes. These results suggest that the restriction element involved in the presentation of GLΦ to B10.A(5R) T cells is composed of a β chain encoded in I‐Ab and an a chain encoded in I‐E for which the allelic products of the k, d, p and r haplotypes are functionally equivalent. This correlation between structure and function represents the strongest evidence so far that Ia antigen‐bearing molecules are the Ir gene products.