The peptide binding specificity of HLA-B27 subtypes.

Five HLA-B27 subtypes, B2701, B2703, B2704, B2705, and B2706, were tested for direct binding with twenty-six synthetic nonapeptides carrying the primary anchor residue motifs (combination of amino residues at positions 2 and 9) relevant to B2705. The peptide sequences were derived from human HSP89 alpha, P53 and MBP. The alpha chains were immunospecifically isolated from LH (B2701), CH (B2703), WE1 (B2704), BTB (B2705), and LIE (B2706) cells and their peptide binding was measured by the HLA class I alpha chain refolding assay. The data obtained indicated that the B27 subtypes tested can bind a common set of peptides carrying several different anchor residue motifs. The motifs, R-K and R-R, reported for B2705 and a new motif H-R were accepted by B2703, B2704, and B2706, but not by B2701. However, other motifs, including known B2702 and/or B2705 motifs, R-H, R-L, R-A, and R-F, and a new motif found here, R-G, were apparently accepted by all B27 subtypes tested. The observed cross-peptide binding in the B27 subgroup is compatible with the so-called arthritogenic peptide hypothesis in the pathogenesis of ankylosing spondylitis.