Genetic control of the immune response to collagen by the major histocompatibility complex in the rat: I. Humoral responses to bovine and chick type II collagen.

A number of congenic and recombinant rat strains with different RT1 haplotypes on a PVG/c background were immunised with native bovine or chick type II collagen. Only strains with the "u" haplotype were good responders to bovine type II collagen whilst all strains responded to chick type II collagen. However, the "u" haplotype was again associated with the production of the highest amounts of antibody. All the strains responded to a non-collagenous antigen, keyhole limpet haemocyanin, showing that this effect was not a general one relating to all antigens. When antibodies were produced to the immunising collagen, binding of antibodies to native rat type II collagen was also seen. This association, of high amounts of antibody with the "u" haplotype, was inherited in a dominant fashion when F1 and F2 hybrids between low responder (RT1a) and high responder (RT1u) were examined. The recombinant r1 (class I av1, class II c) and r8 (class I av1 and class II u) strains showed that "u" haplotype at class II rather than at class I was associated with the strong response to type II collagen. The absence of arthritis in the "u" haplotype rats, suggests that the "u" haplotype alone is insufficient for arthritis induction after immunisation with type II collagen. It suggests that background genes outside the RT1 complex influence arthritis production as Wistar rats with the RT1u haplotype (but different minor genes outside RT1 complex) give an arthritis incidence of 50% under identical immunisation protocols.