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 |
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Authors: | Maria Teresa Fiorillo Giulia Greco Monica Maragno Ilaria Potolicchio Andrea Monizio Maria Luisa Dupuis Rosa Sorrentino |
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Abstract: | 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 --bb--arthritogenic peptide to CD8 T cells. The HLA-B*2709 subtype, although differing by a single amino acid (His116 → Asp116 ) from the wide spread 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. |
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Keywords: | HLA-B27 Ankylosing spondylitis Cytotoxic T lymphocyte Peptide analogue |
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