The South Amerindian allotype HLA-B*3909 has the largest known similarity in peptide specificity and common natural ligands with HLA-B27.
HLA-B*3909 has only been found among South Amerindians, and presumably arose locally in these populations. It differs from B*3901 by a single Tyr to Ser change at position 99. To analyze the influence of this polymorphism on peptide specificity, pool sequence analysis and sequencing of multiple individual ligands from B*3901 and B*3909 were carried out. Both allotypes bind peptides with Arg2 or His2 and nonpolar C-terminal residues. However, whereas His2 is the predominant B*3901 motif, a majority of the B*3909-bound peptides have Arg2. In addition, B*3909 binds peptides with Pro2, and also shows an increased preference for Pro3. In spite of their differences, both subtypes bind overlapping peptide repertoires, as indicated by the identification of several identical ligands from their respective peptide pools. B*3909 is significantly more similar in its peptide specificity to HLA-B27 than B*3901. This is due to the increased preference of B*3909 for Arg2 and to low suitability of HLA-B27 for His2. The similarity between HLA-B27 and B*3909 was confirmed by identification of a natural ligand common to both allotypes. In addition, multiple HLA-B27 ligands bound efficiently B*3909 in vitro. The results indicate that, among the HLA class I allotypes of known peptide specificity, B*3909 is the most similar in its peptide binding properties to HLA-B27, which is absent in South Amerindians. This may have implications for the susceptibility of individuals in these populations to spondyloarthropathies.
Yagüe
J
J
Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, Cantoblanco, Spain.
Ramos
M
M
Vázquez
J
J
Marina
A
A
Albar
J P
JP
López de Castro
J A
JA
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D002460:Cell Line; D005434:Flow Cytometry; D015235:HLA-B Antigens / Q000235:genetics* / Q000378:metabolism*; D015796:HLA-B27 Antigen / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D008969:Molecular Sequence Data; D011485:Protein Binding; D014162:Transfection
D015235:HLA-B Antigens; D015796:HLA-B27 Antigen; D008024:Ligands