The genetic control of antibody specificity

Abstract

The immune response to a synthetic polypeptide built on multichain polyproline, poly-L-(Tyr,Glu)-poly-L-Pro-poly-L-Lys [(T,G)-Pro--L], in the offspring of a cross between DBA/1 and SJL mice is under a genetic control superficially similar to the one operating for the immune response to a similar synthetic polypeptide built on multichain polyalanine, poly-L-(Tyr,Glu)-poly-D,L-Ala-poly-L-Lys [(T,G)-A--L], in the offspring of a cross between CBA and C57 mice. In both cases, the genetic control is a quantitative trait in which the major gene(s) is (are) dominant and the trait is not linked to any of the known structural genes coding for mouse immunoglobulin heavy chains. However, the genetic control of response to (T, G)-Pro--L, designated immune response-3 (Ir-3), is qualitatively different from the one operating for (T,G)-A--L [immune response-1 (Ir-1)] in that it is not linked to the histocompatibility-2 (H-2) locus. A study of the immune response to a related polypeptide built on multichain polyproline, poly-L-(Phe,Glu)-poly-L-Pro-poly-L--Lys [(Phe, G)-Pro--L], in the DBA/1 x SJL cross has shown a genetic control of antibody specificity. F(1) x DBA/1 backcross anti-(Phe, G)-Pro--L sera segregate in their ability to bind (T,G)-Pro--L, and there is no linkage of anti-(T,G)-Pro--L binding capacity with the H-2(s) allele of the SJL grandparent. F(1) x SJL anti-(Phe, G)-Pro-L sera segregate in their capacity to bind poly-L-(Phe,Glu)-poly-D,L-Ala-poly-L-Lys [(Phe, G)-A--L] and the ability to bind (Phe, G)-A--L is clearly linked to the H-2(q) allele from the DBA/1 grandparent. Thus, in mice all responding well to a given antigen [(Phe, G)-Pro--L], the specificity of the antibodies produced [i.e., anti-(Phe,G) or anti-prolyl] is genetically determined. Cross-inhibition of binding m (DBA/1 x SJL)F(1) anti-(Phe,G)-Pro--L antisera indicates that the anti-(Phe,G) and anti-prolyl specificities are a function of two separate and largely non-crossreacting antibody populations.