The primary function of HLA molecules is to present foreign antigens to elicit T cell responses, so the number of distinc HLA allotypes expressed on the cell surface is directly related to the range of foreign antigens the host can present to T cells. Thus, individuals who are heterozygous at the HLA locus will be able to present a broader repertoire of antigenic peptides to T cells as compared to homozygotes, thereby exerting greater pressure on the pathogen to escape the cytotoxic T lymphocyte responses that may in turn affect pathogen fitness. Under this model, it would be expected that HLA homozygous individuals would progress more rapidly to AIDS than HLA heterozygous individuals after HIV infection. Indeed, a highly significant association of HLA class I homozygosity with rapid progression to AIDS in both Caucasians and African Americans was demonstrated and the three class I loci contributed independently to the association, and the effect was most pronounced in individuals who were homozygous at two or three.
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