The role of HLA molecules is to present peptides from invasive organisms, and the genes of the MHC are the most polymorphic of the human genome (total HLA alleles 13.023; HLA class I allelles 9749 and HLA classs II alleles 3274). Therefore it is likely that this extreme polymorphysm has evolved as a mechanism for coping with all of the different peptides that will be encountered. HLA molecules differs slightly from each other in its amino acid sequence (different HLA antigens) which causes different structure in the peptide-binding-cleft. The distal membrane domains present a higher degree of variability, whereas the proximal membrane domains as well as the trans-membrane and cytoplasmic domains have limited or no polymorphism. This explained by the fact that the vast majority of the nucleotide polymorphysms occur in exon 2 of the HLA class II genes and in exons 2 and 3 of the HLA class I genes.
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