DETERMINANT-SPECIFIC REGULATION OF T-HELPER CELL RESPONSES TO MURINE LAMBDA-LIGHT CHAINS BY BOTH H-2 AND NON-H-2 GENES

Previous work has revealed that the T helper cell (Th) responses to an antigenic determinant of V.lambda.2315 (called .lambda.2.1) is regulated by both H-2 and non-H-2 genes. In this study this was confirmed and extended to 2 other determinants, 1 shared between free .lambda.2315 and .lambda.1J558 (called .lambda.2.2) and 1 unique for free .lambda.1J558 (called .lambda.1.1). H-2 genes regulate the responses to the latter determinants because BALB.B (H-2b) mice were low responders and BALB/c (H-2d) mice were high responders. Thus, the H-2d haplotype on BALB/c background was associated with high responder status. When the H-2d haplotype was examined on other genetic backgrounds than BALB/c, the animals could be classified as either intermediate or low responders, depending upon the non-H-2 background. This demonstrated that non-H-2 genes also influenced Th responses. C3H-H-20, DBA/2 and B10.D2 mice (all H-2d) responded to only 1 (.lambda. 2.1) but not the other (.lambda.2.2) of 2 determinants physically linked on the same polypeptide chain (.lambda.2315). This indicated that the non-H-2 gene effect is capable of fine discrimination, i.e., the non-H-2 gene-mediated low responder phenotype may at least in part be due to failure of recognition of certain antigenic sites, like the H-2-linked Ir-gene defect. F1 hybrids responded to the same determinants as their parental strains; e.g., the BALB/c non-H-2 background exerted a dominant influence over the low responder background of C3H, B10 and DBA/2 strains.