Structure and regulation of immunoglobulins: kappa allotypes in the rat have multiple amino-acid differences in the constant region

Abstract

Immunoglobulin kappa chains from various inbred strains of rats have two serologically detectable forms that segregate in a Mendelian fashion (allotypes a and b of the RI-I locus). Partial amino-acid sequences from the constant regions of these two forms have been compared. Of the 81 residues of the constant region studied, 10 amino-acid substitutions as well as one size difference (sequence gap) were found. This large number of sequence differences among alternative forms of the kappa allotype raises provocative questions as to the genetic and evolutionary implications of these light chain allotypes. We designate allotypes whose alternative forms differ at multiple residue positions as complex allotypes. There are basically two genetic models that might explain complex allotypes. First, these allotypes are alleles of a single structural gene with an unusual evolutionary history. Second, all rats have genes that code for each of the light chain allotypes and a control mechanism that permits them to be expressed so that they mimic a Mendelian pattern of segregation. We discuss evidence from other immunoglobulin systems that is compatible with this second model.