RELEVANCE OF RESIDUE-116 OF HLA-B27 IN DETERMINING SUSCEPTIBILITY TO ANKYLOSING-SPONDYLITIS

Ankylosing spondylitis (AS) is an autoimmune disorder strongly associa ted with HLA-B27. A direct role of B27 molecules in the disease pathog enesis has been postulated, possibly by presenting to T cells an as-ye t unidentified arthritogenic peptide that triggers the autoimmune resp onse. There are nine HLA-B27 alleles differing from each other at one or more amino acid positions. It is important, for the identification of the arthritogenic peptide, to define which alleles, and therefore w hich polymorphic positions, predispose to the disease. Here, we report that HLA-B2709 is not associated with AS, as it was not found in pat ients. HLA-B2709 differs from the most frequent and disease-associate d HLA-B2705 allele for a single substitution (His vs. Asp) at positio n 116. Amino acid 116 is located at the bottom of the groove where the antigenic peptide sits, and it has been proven to influence the pepti de-binding specificity of HLA class I molecules. The most likely inter pretation of these data is that the differences in charge and size tha t accompany the His-to-Asp substitution exclude the acceptance of the arthritogenic peptide.