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 2(315) (called lambda 2.1) is regulated by both H-2 and non-H-2 genes. In the present study this was confirmed and extended to two other determinants, one shared between free lambda 2(315) and lambda 1(J558) (called lambda 2.2) and one unique for free lambda 1(J558) (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. However, 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. Furthermore, C3H-H-2o, DBA/2 and B10.D2 mice (all H-2d) responded to only one (lambda 2.1) but not the other (lambda 2.2) of two determinants physically linked on the same polypeptide chain (lambda 2(315)). 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.