Ir-LDHB: map position and functional analysis.

Abstract

AbstractDifferent strains of mice immunized with lactic dehydrogenase B (LDHB) can be classified into high and low responders. Breeding experiments suggest regulation of this immune response by a dominant gene (Ir‐LDHB), which is linked to the major histocompatibility complex (H‐2). Studies in recombinant inbred mice made it possible to map Ir‐LDHB 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)‐LDHB was used as a hapten‐carrier complex, demonstrated that LDHB‐specific helper activity was detectable in LDHB‐primed spleen cells of responder animals only. This indicates a deficiency of LDHB‐specific T cells in low responder mice.Immunization of congenic mice with the hybrid isoenzyme LDHAB results in equal production of anti‐LDHB 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‐LDHB 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‐LDHB is expressed exclusively at the level of T cell function.