The peptide repertoires of HLA-B27 subtypes differentially associated to spondyloarthropathy (B*2704 and B*2706) differ by specific changes at three anchor positions.
HLA-B*2704 is strongly associated with ankylosing spondylitis. B*2706, which differs from B*2704 by two amino acid changes, is not associated with this disease. A systematic comparison of the B*2704- and B*2706-bound peptide repertoires was carried out to elucidate their overlap and differential features and to correlate them with disease susceptibility. Both subtypes shared about 90% of their peptide repertoires, consisting of peptides with Arg(2) and C-terminal aliphatic or Phe residues. B*2706 polymorphism influenced specificity at three anchor positions: it favored basic residues at P3 and POmega-2 and impaired binding of Tyr and Arg at POmega. Thus, the main structural feature of peptides differentially bound to B*2704 was the presence of C-terminal Tyr or Arg, together with a strong preference for aliphatic/aromatic P3 residues. This is the only known feature of B*2704 and B*2706 that correlates to their differential association with spondyloarthropathy. The concomitant presence of basic P3 and POmega-2 residues was observed only among peptides differentially bound to B*2706, suggesting that it impairs binding to B*2704. Similarity between peptide overlap and the degree of cross-reaction with alloreactive T lymphocytes suggested that the majority of shared ligands maintain unaltered antigenic features in the context of both subtypes.
Sesma
Laura
L
Centro de Biologia Molecular Severo Ochoa, Universidad Autónoma de Madrid, Facultad de Ciencias, 28049 Madrid, Spain.
Montserrat
Verónica
V
Lamas
Jose Ramón
JR
Marina
Anabel
A
Vázquez
Jesús
J
López de Castro
José A
JA
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000378:metabolism; D001120:Arginine / Q000737:chemistry; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid; D000939:Epitopes / Q000737:chemistry; D015796:HLA-B27 Antigen / Q000737:chemistry*; D006801:Humans; D007126:Immunoglobulin Allotypes / Q000737:chemistry; D008024:Ligands; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry*; D010649:Phenylalanine / Q000737:chemistry; D011110:Polymorphism, Genetic; D017434:Protein Structure, Tertiary; D013166:Spondylitis / Q000276:immunology / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000378:metabolism; D014443:Tyrosine / Q000737:chemistry
D000911:Antibodies, Monoclonal; D000939:Epitopes; D015796:HLA-B27 Antigen; D007126:Immunoglobulin Allotypes; D008024:Ligands; D010455:Peptides; D014443:Tyrosine; D010649:Phenylalanine; D001120:Arginine