Variable mapping of H-2 genes controlling the T-cell response to antigenic determinants of insulin

Abstract

The object of the studies reported here was to map the genes regulating the proliferative response of T lymphocytes to the antigenic determinants of pork and sheep insulins and to locate the genes complementing the response to sheep, pork, or beef insulins. The results of these studies indicate that non-H-2 genes can influence the mapping of the H-2 alleles critical for a response to a particular antigenic determinant. Furthermore, H-2 complementation for a response to one antigenic determinant may be at the expense of the potential to respond to another antigenic determinant. These findings emphasize the provisional nature of the selection of antigenic determinants by H-2-gene products. Table 1 shows H-2 mapping of the T-cell proliferative response to sheep insulin. One can see (IA) that for a response to occur in mice bearing the B10 background, there was a need for k alleles throughout the H-2 complex or for k alleles to the left of I-E and to the right of H-2K, in combination with d alleles to the right of the I-E subregion. The possible contribution of these d alleles is unclear and cannot be resolved with the kid recombinants presently available. The Ir genes responsible for the response to sheep insulin in strains with the A genetic background are mapped in Table lB. A/J mice similar to B10.BR, B10.A, and B10.AQR mice were high responders. A.AL and A.TL mice were low responders, even though they possessed k alleles throughout the I region. The differences between A.AL, A.TL, and the responder strain A/J is that A/J has d alleles to the right of I-E and to the left of H-2D. Hence, it seems that a response to sheep insulins in mice with the A genetic background was controlled either by d alleles mapped to the region between I-E and H-2D or to complementation involving k alleles and d alleles. The notion of complementation was supported by