The peptide binding specificity of HLA-B27 subtypes.
Five HLA-B27 subtypes, B*2701, B*2703, B*2704, B*2705, and B*2706, 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 B*2705. The peptide sequences were derived from human HSP89 alpha, P53 and MBP. The alpha chains were immunospecifically isolated from LH (B*2701), CH (B*2703), WE1 (B*2704), BTB (B*2705), and LIE (B*2706) 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 B*2705 and a new motif H-R were accepted by B*2703, B*2704, and B*2706, but not by B*2701. However, other motifs, including known B*2702 and/or B*2705 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.
Istituto di Biologia Cellulare, CNR, Roma, Italy.
N
N
Tanigaki
D
D
Fruci
E
E
Vigneti
G
G
Starace
P
P
Rovero
M
M
Londei
R H
RH
Butler
R
R
Tosi
D000595:Amino Acid Sequence; D001120:Arginine / Q000378:metabolism; D002460:Cell Line; D015796:HLA-B27 Antigen / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000138:chemical synthesis / Q000378:metabolism*; D011485:Protein Binding; D017510:Protein Folding
D015796:HLA-B27 Antigen; D009842:Oligopeptides; D001120:Arginine