Hierarchy ofH-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 underH-2 control. On the C57BL/10 (B10) background,H-2^b andH-2^d strains of mice are high responders, whereasH-2^a,H-2^k orH-2^y2 strains yield low levels of indirect TNP-specific PFC. An unusual pattern of inheritance has been revealed in B10 congenic mice: high responsiveness controlled byH-2^b is inherited recessively, while high responsiveness controlled byH-2^d is inherited dominantly. On the C3H and A strain backgrounds, high responsiveness controlled byH-2^b is partially recessive;H-2^b/H-2^a F₁ mice respond with 20%-40% of the high responderH-2^b response. Yet, high responsiveness controlled by theH-2^d 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-2^d>H-2^b>H-2^k,H-2^a orH-2^y2. The unusual patterns of inheritance in the TNP-MSA system reveal graded regulation of responsiveness attributable to bothH-2 and non-H-2 genes.