Large sharing of T-cell epitopes and natural ligands between HLA-B27 subtypes (B*2702 and B*2705) associated with spondyloarthritis

Tissue Antigens
M MartiJ A Lopez de Castro

Abstract

HLA-B*2702 is an ankylosing spondylitis-associated allotype that differs from the more common B*2705 at residues 77, 80, and 81, in the peptide-binding site. The diversity and fine specificity of alloreactive cytolytic T-lymphocyte (CTL) raised against B*2702 were analyzed at the clonal level. Significant crossreaction with B*2705 and B*2709 indicated that the three subtypes share numerous T-cell epitopes. However, some epitopes shared by B*2702 and B*2705 were lost in B*2709, which correlates with weaker association of this subtype to disease. Clonal specificities were donor-dependent, indicating that allo-immunogenicity is variable among individuals. Anti-B*2702 CTL were little affected by single mutations mimicking B*2702/B*2705 polymorphism, but the double mutant at positions 77 and 81 was recognized worse than B*2705, suggesting a compensatory effect of residue 80. Thus, HLA-B27 polymorphism modulated alloreactivity through cooperative and compensatory effects on T-cell epitope structure. Comparison of B*2705- and B*2702-bound peptide repertoires revealed that they overlapped by 73% and 81%, respectively. This was larger than B*2702/B*2705 cross-reaction, indicating that HLA-B27 allospecificity is only partially determined...Continue Reading

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Citations

Nov 26, 2002·Tissue Antigens·M Ramos, J A López de Castro
Apr 24, 2004·Tissue Antigens·J A Lopez de CastroM Vázquez
Oct 1, 2014·PloS One·Alejandro BarrigaDaniel López
Nov 9, 2018·Immunology·Anna Mestre-FerrerIñaki Alvarez
May 22, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Veronica MontserratJosé A López de Castro
Jun 10, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Laura SesmaJosé A López de Castro

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