Molecular Polymorphism of Human Immune-Response-Genes

Abstract

The observations that in mice the humoral response to a specific antigenic challenge is in some instances genetically controlled [49], and that the genetic loci responsible for this modulation of the murine immune response map to the class II region within the major histocompatibility complex (MHC) [7], have led to the conclusion that the I region in mice and the D region in man encode at least some of the immune-response (Ir) genes. Understanding the structure and polymorphism of the genes within these regions has therefore become an important priority among those studying the genetic basis of the immune response. The original observations on the function of Ir genes have been substantially broadened, so that these genes are now acknowledged to govern the response to a wide variety of antigenic challenges and to control both humoral and cell-mediated immune responses [72]. In man, there is now evidence that these genes function in a similar manner to regulate immune responsiveness [67, 68] and map to the class II region of the MHC. The products of this region are highly polymorphic, and it is likely that these polymorphisms are responsible for the variability observed between individuals in immune responsiveness. An understanding of structural differences between alleles of the class II loci is an important step toward understanding the molecular basis of immune responsiveness. An additional by-product of such studies may be to reveal how the genes of the class II region have acquired and maintained such extensive amounts of polymorphism.