High T cell epitope sharing between two HLA-B27 subtypes (B*2705 and B*2709) differentially associated to ankylosing spondylitis.

Abstract

HLA-B*2705 is strongly associated with ankylosing spondylitis (AS) and reactive arthritis. In contrast, B*2709 has been reported to be more weakly or not associated to AS. These two molecules differ by a single amino acid change: aspartic acid in B*2705 or histidine in B*2709 at position 116. In this study, we analyzed the degree of T cell epitope sharing between the two subtypes. Ten allospecific T cell clones raised against B*2705, 10 clones raised against B*2703 but cross-reactive with B*2705, and 10 clones raised against B*2709 were examined for their capacity to lyse B*2705 and B*2709 target cells. The anti-B*2705 and anti-B*2703 CTL were peptide dependent as demonstrated by their failure to lyse TAP-deficient B*2705-T2 transfectant cells. Eight of the anti-B*2705 and five of the anti-B*2703 CTL clones lysed B*2709 targets. The degree of cross-reaction between B*2705 and B*2709 was donor dependent. In addition, the effect of the B*2709 mutation (D116H) on allorecognition was smaller than the effect of the other naturally occurring subtype change at this position, D116Y. These results demonstrate that B*2705 and B*2709 are the antigenically closest HLA-B27 subtypes. Because allospecific T cell recognition is peptide dependent, our results imply that the B*2705- and B*2709-bound peptide repertoires are largely overlapping. Thus, to the extent to which linkage of HLA-B27 with AS is related to the peptide-presenting properties of this molecule, our results would imply that peptides within a relatively small fraction of the HLA-B27-bound peptide repertoire influence susceptibility to this disease.

• Authors: M García-Peydró, M Martí, J A López de Castro
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 163 Issue 4 Pg. 2299-305 (Aug 15 1999) ISSN: 0022-1767 [Print] United States
• PMID: 10438975 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Epitopes, T-Lymphocyte
• HLA-B27 Antigen
• Peptides

Topics

• Alleles
• Amino Acid Substitution (genetics, immunology)
• Clone Cells
• Cytotoxicity Tests, Immunologic
• Epitopes, T-Lymphocyte (genetics, immunology)
• HLA-B27 Antigen (genetics, immunology)
• Humans
• Peptides (genetics, immunology)
• Point Mutation
• Spondylitis, Ankylosing (genetics, immunology)
• T-Lymphocytes, Cytotoxic (immunology, metabolism)
• Transfection