HLA Structure and Function: A Contemporary View

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Abstract
The HLA and H-2 genetic maps are aligned optimally if HLA-A corresponds to H-2K, in which case the position of all the other markers, except these, corresponds. The two sequences could be related by a double inversion, an intra-chromosomal double crossover, or differential expression of different parts of the regions in the two species. The coding regions of DNA are probably arranged into non-contiguous pieces, which may correspond to defined domains of the HLA protein products. Serological data suggest an ABC common region which codes for a piece common to the HLA-A,B and C products and raises the question of control of expression over relatively long distances. Trophoblasts and so choriocarcinomas do not express HLA-A,B,C on their surface and this may explain why the fetus survives as an allograft and why HLA incompatibility does not affect choriocarcinomas. The lack of expression of HLA-A,B,C on some tumors may be a change that is selected for during tumor progression to escape from T cell mediated immune attack. The mouse H-2 I-A region probably corresponds to the neighborhood of HLA-DR, while the apparent heterogeneity of the HLA-DR products may be explained by the existence of two or more sets of products homologous to I-A and I-E/C. HLA-A,B,C and DR products may behave like complement components on the cell surface in relation to the T-cell receptor. This suggestion has interesting implications for the function of the T-cell receptor, the nature of antigen specific factors and their role in autoimmune disease. The HLA region as a whole may code for up to 150 peptides of the approximate size of the HLA-A,B and C products.