H‐2 genetic control of the response of T lymphocytes to insulins. Priming of nonresponder mice by forbidden variants of specific antigenic determinants

Abstract H‐2 gene control of the response of T lymphocytes to antigenic determinants of ungulate insulins has been studied. We injected H‐2‐congenic mice with different insulins emulsified in complete Freund's adjuvant and measured the proliferative response in vitro of the draining lymph node cells to various related insulins. Two groups of determinants were antigenic: the A chain loop determinant present on bovine and sheep insulins, but absent on pig insulin, and a pig‐associated determinant(s) also shared by bovine and sheep insulins. The responses to these two sets of determinants were controlled by H‐2 genes as follows: (a) The pig‐associated determinant(s) was antigenic for H‐2 d but not for H‐2′ or H‐2 k mice. (b) The A chain loop determinant was immunodominant over the pig‐associated determinant(s) for H‐2 d mice. In the presence of the A chain loop determinant, H‐2 d mice did not respond to the pig‐associated determinant(s) on the same molecule. (c) H‐2 d mice did not distinguish between the bovine and sheep variants of the A chain loop that differed by substitution of one amino acid. (d) In contrast, H‐2 k mice responded only to the sheep variant, while H‐2 b mice responded primarily to the bovine variant of the A chain loop determinant. (e) However, injection of H‐2 b mice with “forbidden” sheep insulin primed them for an in vitro response to the “permitted” bovine variant of the A chain loop determinant. Similarly, some H‐2 k mice injected with forbidden bovine insulin responded in vitro to the permitted sheep variant of the A chain loop determinant. Thus, H‐2 gene products decided whether the immune response would express an affinity for the specific immunizing antigen itself and/or for a closely related variant.