Hierarchy of H-2 haplotypes governs inheritance of immune responsiveness to TNP-MSA

Production of indirect TNP-specific plaque-forming cells (PFC) in response to immunization with 2, 4, 6-trinitrophenyl (TNP) conjugated to autogenous mouse serum albumin (MSA) in complete Freund's adjuvant (CFA) is under H-2 control. On the C57BL/10 (B10) background, H-2b and H-2d strains of mice are high responders, whereas H-2a, H-2k or H-2y2 strains yield low levels of indirect TNP-specific PFC. An unusual pattern of inheritance has been revealed in B10 congenic mice: high responsiveness controlled by H-2b is inherited recessively, while high responsiveness controlled by H-2d is inherited dominantly. On the C3H and A strain backgrounds, high responsiveness controlled by H-2b is partially recessive;H-2b/H-2a F1 mice respond with 20%-40% of the high responder H-2b response. Yet, high responsiveness controlled by the H-2d haplotype remains dominant on the C3H background. A hierarchy of haplotypes in order of decreasing immune responsiveness to TNP-MSA is evident as follows:H-2d>H-2b>H-2k, H-2a or H-2y2. The unusual patterns of inheritance in the TNP-MSA system reveal graded regulation of responsiveness attributable to both H-2 and non -H-2 genes. © 1980 Springer-Verlag.