The considerable polymorphysm of HLA is well known. With serologic analysis, for example, at least 25 alleles have been reported for HLA-A, 60 alleles for HLA-B, and 18 alleles for HLA-DR. Molecular typing has resulted in identification of even much greater numbers of HLA alleles, and it is often difficult to find perfectly HLA-matched unrelated donor organs for transplantation. The polymorphysim of HLA is reflected by variations in amino acid sequences of HLA molecules. Differences in the amino acid composition of the peptic binding site alter the spectrum of antigenic peptides presented by HLA molecules, which affects the repertoire of responding T cells. This concept may explain why many autoimmune diseases, such as juvenile diabetes and rheumatoid arthritis, are associated with specific HLA types.
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