The naturally occurring polymorphism Asp116-->His116, differentiating the ankylosing spondylitis-associated HLA-B*2705 from the non-associated HLA-B*2709 subtype, influences peptide-specific CD8 T cell recognition.
HLA-B27 molecules are interesting because of their strong association with ankylosing spondylitis (AS) and reactive arthritis (ReA). A pathogenetic role for these molecules has been postulated in presenting a putative "arthritogenic" peptide to CD8 T cells. The HLA-B*2709 subtype, although differing by a single amino acid (His116-->Asp116) from the widespread and strongly AS-associated subtype HLA-B*2705, is not found in patients. Since residue 116 interacts with the C terminus of the peptide, it is possible that the two subtypes differ in their antigen-presenting features. We show here that CD8 T cells can distinguish the two HLA-B27 subtypes when presenting a same epitope derived from Epstein-Barr virus-latent membrane protein 2. Moreover, alanine scanning mutagenesis analysis revealed that the peptide residues relevant for such recognition are different depending on whether HLA-B*2705 or -B*2709 molecules present the epitope. These results give support to the belief that functional differences determined by subtype-specific polymorphisms can have a pathogenetic relevance and open up a new scenario where subtle modifications within the peptide/HLA ligand might be responsible for the differential association between HLA-B27 subtypes and spondyloarthropathies.
Fiorillo
M T
MT
Department of Cell Biology and Development, University of Rome La Sapienza, Roma, Italy.
Greco
G
G
Maragno
M
M
Potolicchio
I
I
Monizio
A
A
Dupuis
M L
ML
Sorrentino
R
R
D000595:Amino Acid Sequence; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D015796:HLA-B27 Antigen / Q000235:genetics*; D006801:Humans; D009842:Oligopeptides / Q000235:genetics / Q000276:immunology; D011110:Polymorphism, Genetic; D000091402:Prohibitins; D013167:Spondylitis, Ankylosing / Q000235:genetics* / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014162:Transfection; D014763:Viral Matrix Proteins / Q000235:genetics / Q000276:immunology
C037662:EBV-associated membrane antigen, Epstein-Barr virus; D015796:HLA-B27 Antigen; D009842:Oligopeptides; C000717331:PHB2 protein, human; D000091402:Prohibitins; D014763:Viral Matrix Proteins