Ir‐LDHB: Map position and functional analysis

Different strains of mice immunized with lactic dehydrogenase B (LDH B ) can be classified into high and low responders. Breeding experiments suggest regulation of this immune response by a dominant gene (Ir‐LDH B ), which is linked to the major histocompatibility complex (H‐2). Studies in recombinant inbred mice made it possible to map Ir‐LDH B within the H‐2 complex between Ir‐1 and Ss‐Slp. The argument that it is a single gene or only a small gene cluster which regulates immune responsiveness to the multideterminant enzyme molecule is strengthened by our finding of only two levels of responsiveness among a variety of inbred mouse strains. Responsiveness in this system is thymus‐dependent and can be transferred to low responders by transfer of normal or immune spleen cells from high responders. Experiments in an adoptive transfer system, in which 4‐hydroxy‐5‐iodo‐3‐nitrophenacetyl (NIP)‐LDH B was used as a hapten‐carrier complex, demonstrated that LDH B ‐specific helper activity was detectable in LDH B ‐primed spleen cells of responder animals only. This indicates a deficiency of LDH B ‐specific T cells in low responder mice. Immunization of congenic mice with the hybrid isoenzyme LDH AB results in equal production of anti‐LDH B antibodies in low and high responders. Examination of these sera in isoelectric focussing (IEF) led to the following conclusions. a) Individual sera show, in general, little heterogeneity of anti‐LDH B antibodies. b) Low responders exhibit a similar degree of heterogeneity as do high responders. c) A few groups of bands, indistinguishable in IEF, appear repeatedly in individual sera, irrespective of the H‐2 allele of the donor. We conclude that Ir‐LDH B is expressed exclusively at the level of T cell function.