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
✍ Scribed by Maria Teresa Fiorillo; Giulia Greco; Monica Maragno; Ilaria Potolicchio; Andrea Monizio; Maria Luisa Dupuis; Rosa Sorrentino
- Publisher
- John Wiley and Sons
- Year
- 1998
- Tongue
- English
- Weight
- 155 KB
- Volume
- 28
- Category
- Article
- ISSN
- 0014-2980
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✦ Synopsis
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 (His 116 1 Asp 116 ) 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 viruslatent 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.