THE PEPTIDE BINDING-SPECIFICITY OF HLA-B27 SUBTYPES

Five HLA-B27 subtypes, B2701, B*2703, B*2704, B*2705, and B*2706, wer e tested for direct binding with twenty-six synthetic nonapeptides car rying 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 imm unospecifically isolated from LH (B2701), CH (B*2703), WEI (B*2704), BTB (B2705), and LIE (B*2706) cells and their peptide binding was mea sured by the HLA class I alpha chain refolding assay. The data obtaine d indicated that the B27 subtypes tested can bind a common set of pept ides 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 B*2 703, B2704, and B*2706, but not by B*2701. However, other motifs, inc luding known B2702 and/or B*2705 motifs, R-H, R-L, R-A, and R-E and a new motif found here, R-G, were apparently accepted by all B27 subtyp es tested. The observed cross-peptide binding in the B27 subgroup is c ompatible with the so-called arthritogenic peptide hypothesis in the p athogenesis of ankylosing spondylitis.