COMPLEX INTERPLAY OF HLA POLYMORPHISM AND DISEASE ASSOCIATION

Abstract

HLA (human leucocyte antigen) system or human major histocompatibility complex (MHC) is the most polymorphic functional genetic -entity known at present (Charron and Khalil, 1994). lt consist of 3 classes, class I genes and its molecules A, B and C

(Carosella et al., 1996), class li genes and its molecules DR, DP and DQ (Beck et al., 1996) and class III genes (David et al., 1995). Each of these molecules exists in multiple different allelic fonns (Brown et al., 1993), that• is, a given copy of chromosome 6 can contain anyone of many alternative versiOns of each gene, that yield proteins with distinct sequences (Goodman, 1996).

Because of the extreme polymorphism of these loci, the probability that any 2 individuals will express identical sets of HLA protein is very low (Rowis and Trowsdale, 1994). Almost all of the polymorphic residues i.e. those aminoacids found to vary

among different allelic forms, are located either in the a helical sides of the cleft or on thestrands of the HLA molecules that form the floor of the cleft (Albert et al., 1994). The genetic polymorphism ofMHC 'Class I and class li molecules determine the chemical surface of the cleft and is the principle detenninant of the specificity and affinity of peptide-binding.and T cell recognition (Parham, 1992). A high level of polymorphism is needed to prevent the emergence of microbial peptides that cannot bind to any MHC class I or class II molecules (Sloan et al., I 998). On the population level, the MHC gene secu es the integrity and individuality of an organism and as the last consequence, survival of the species (Parham, 1992).