THE NATURALLY-OCCURRING POLYMORPHISM ASP(116)-]HIS(116), DIFFERENTIATING THE ANKYLOSING SPONDYLITIS-ASSOCIATED HLA-B-ASTERISK-2705 FROM THENONASSOCIATED HLA-B-ASTERISK-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 patho genetic role for these molecules has been postulated in presenting a p utative ''arthritogenic'' peptide to CD8 T cells. The HLA-B2709 subty pe, although differing by a single amino acid (His(116) --> Asp(116)) from the widespread and strongly AS-associated sub type HLA-B2705, is not found in patients. Since residue 116 interacts with the C terminu s of the peptide, it is possible that the two subtypes differ in their antigen-presenting features. We show here that CD8 T cells can distin guish the two HLA-B27 subtypes when presenting a same epitope derived from Epstein-Barr virus-latent membrane protein 2. Moreover, alanine s canning mutagenesis analysis revealed that the peptide residues releva nt for such recognition are different depending on whether HLA-B2705 or -B2709 molecules present the epitope. These results give support t o the belief that functional differences determined by subtype-specifi c polymorphisms can have a pathogenetic relevance and open up a new sc enario where subtle modifications within the peptide/HLA ligand might be responsible for the differential association between HLA-B27 subtyp es and spondyloarthropathies.