Immunoglobulin GM and KM allotypes and vaccine immunity

Immunoglobulin (Ig) GM and KM allotypes are genetic markers of gamma and ka ppa -type light chains, respectively. The striking qualitative and quantita tive differences in the distribution of these determinants among different races raise questions concerning the nature of the evolutionary selective m echanism that maintains this variation. Associations between Ig allotypes a nd specific antibody responses could be a selective force for the maintenan ce of various haplotypes and their frequencies. Data from several studies r eporting significant associations between certain GM and KM allotypes and i mmune responsiveness to polysaccharide vaccines and to particular infectiou s pathogens support this hypothesis. Possible ways in which constant (C)-re gion allotypes could contribute to the antibody specificity include the fol lowing: (i) certain alleles coding for allotypes may be in linkage disequil ibrium with particular variable (V)-region determinants associated with imm une responsiveness; (ii) they could directly contribute to the formation of specific idiotypes, as shown for the T15 system in mice; and (iii) allotyp e-associated structural variability in the C-region could modulate the kine tic competence of the antigen binding sites. (C) 2000 Elsevier Science Ltd. All rights reserved.