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

Details

Serval ID
serval:BIB_F1AC57B680D7
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
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
Journal
European Journal of Immunology
Author(s)
Fiorillo  M. T., Greco  G., Maragno  M., Potolicchio  I., Monizio  A., Dupuis  M. L., Sorrentino  R.
ISSN
0014-2980 (Print)
Publication state
Published
Issued date
08/1998
Volume
28
Number
8
Pages
2508-16
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Aug
Abstract
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 (His116-->Asp116) 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 virus-latent 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.
Keywords
Amino Acid Sequence CD8-Positive T-Lymphocytes/*immunology Cell Line Cytotoxicity, Immunologic HLA-B27 Antigen/*genetics Humans Oligopeptides/genetics/immunology *Polymorphism, Genetic Spondylitis, Ankylosing/*genetics/*immunology T-Lymphocytes, Cytotoxic/immunology Transfection Viral Matrix Proteins/genetics/immunology
Pubmed
Web of science
Create date
25/01/2008 15:16
Last modification date
20/08/2019 16:19
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