Susceptibility to ankylosing spondylitis correlates with the C-terminal residue of peptides presented by various HLA-B27 subtypes.
Susceptibility to spondyloarthropaties is strongly associated with some HLA-B27 alleles. Evidence suggests a direct pathogenic role for the B27 molecules which possibly present an arthritogenic peptide to the T cells. If this hypothesis is true, B27 subtypes that differ structurally but are disease-associated ought to be capable of presenting such peptide(s), while non-disease-associated ones would not. We have recently described a B27 subtype, B*2709, and shown its absence in ankylosing spondylitis (AS) patients. Here, we show the elution and sequence of peptides from HLA-B*2709 molecules. Similar to other B27 subtypes, these peptides are mainly nonamers with an Arg at position P2. Comparison of the C-terminal anchors of peptides eluted from B*2702 and B*2705 with those eluted from B*2709 reveals that, while B*2702 and B*2705 have a broader specificity, B*2709 molecules appear to only accept C-terminal hydrophobic residues. A common feature shared by the two caucasoid AS-associated subtypes (B*2702 and B*2705) but different from B*2709, is the presence of a Tyr as peptide C-terminal anchor. The substitution of Val for Tyr at the C terminus in one of the eluted peptides greatly reduces the binding to B*2709 molecules. This finding suggests Tyr as a discriminative amino acid allowed at the C terminus of peptides bound to the AS-associated B27 subtypes, but not to those which are not associated with AS.
Fiorillo
M T
MT
Department of Cell Biology and Development, University of Rome La Sapienza, Italy.
Meadows
L
L
D'Amato
M
M
Shabanowitz
J
J
Hunt
D F
DF
Appella
E
E
Sorrentino
R
R
D000595:Amino Acid Sequence; D017951:Antigen Presentation / Q000235:genetics*; D002461:Cell Line, Transformed; D004198:Disease Susceptibility; D015796:HLA-B27 Antigen / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D010455:Peptides / Q000737:chemistry / Q000235:genetics*; D011487:Protein Conformation; D013167:Spondylitis, Ankylosing / Q000235:genetics*; D014162:Transfection
D015796:HLA-B27 Antigen; D010455:Peptides