Possible assortment of a1 and a2 region gene segments in human MHC class I molecules

Abstract

Using pair-wise comparison of aligned nucleotide sequences of distinct and complete human MHC class I molecules, we have constructed triangular tables to study the similarities and differences of various a1 (exon 2) and a2 (exon 3) region sequences. There are two HLA-A (A*6901 and A*6601) and 13 HLA-B (B*4201, B*8101, B*4102, B*4801, B*4007, B*4001, B*4802, Dw53, B*4406, B*4402, B*3901, B*1514 and B*3702) sequences that have identical a1 sequences with other known MHC class I molecules, while their a2 sequences are the same as those of different ones. Of these 15, A*6901, B*4001 and B*4802 have previously been suggested as the results of recombination between A*6801 and A*0201, B*4101 and B*8101, and B*4801 and B*3501, respectively. However, many other sequences can also be used to generate them by recombination. Furthermore, their reciprocal products have never been identified. Thus, gene conversion has subsequently been suggested as an alternative. Another possible genetic mechanism for generating these nucleotide sequence similarities can be assortment, or that some gene segments can be duplicated or multiplicated to be used in different human MHC class I molecules. Interestingly, this genetic mechanism is probably absent for the generation of different mouse MHC class I molecules.