T-Cell Responses Against Viral and Self-Epitopes and HLA-B27 Subtypes Differentially Associated with Ankylosing Spondylitis

  • María T. Fiorillo
  • Rosa Sorrentino
Part of the Advances in Experimental Medicine and Biology book series (volume 649)


HLA-B27 family comprehends some alleles strongly associated with Ankylosing Spondylitis (AS) and some others that are not. A comparative analysis at genetic and functional level is likely to give a clue to the understanding of disease pathogenesis. Here, we summarize our recent studies on the functional differences between B*2705, the most frequent and worldwide AS-associated allele and B*2709, an allele found in Sardinia where it accounts for 20% of all B27 alleles and where it is not associated with AS. The two B27 alleles are distinguished by a single amino acid change, located in the peptide binding groove, that correlates with relevant structural and functional differences in presenting viral and self peptides to T-cells. In particular, B*2709 individuals lack in their T-cell repertoire of CD8+ T-cells specific for a self-epitope (pVIPR) derived from the vasoactive intestinal peptide Type 1 receptor (VPAC1). This peptide shares extensive homology with a viral epitope, pLMP2, derived from EBV, toward which, both B*2705 and B*2709 individuals mount a vigorous CTL response. A likely explanation to this finding, also supported by crystallographic data, is that the autoreactivity present in the disease-prone B*2705 individuals can be unleashed by a molecular mimicry mechanism which does not occur in the B*2709 individuals. The possible implications of the T-cell cross-reactivity between pLMP2, pVIPR and other related peptides in AS pathogenesis are discussed.


Ankylose Spondylitis Single Amino Acid Change Peptide Binding Groove Degree Ofsimilarity Molecular Mimicry Mechanism 
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Copyright information

© Landes Bioscience and Springer Science+Business Media 2009

Authors and Affiliations

  • María T. Fiorillo
    • 1
  • Rosa Sorrentino
    • 1
  1. 1.Department of Cell Biology and Development, “Sapienza”Università di RomaRomaItaly

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