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Susceptibility to rheumatoid arthritis maps to a T-cell epitope shared by the HLA-Dw4 DR beta-1 chain and the Epstein-Barr virus glycoprotein gp110.

Abstract
Rheumatoid arthritis is associated with the HLA antigen HLA-DR4. Disease susceptibility maps to the amino acid sequence QKRAA located in the third hypervariable region of the DR beta-1 chain. This region is thought to be a site of recognition for the T-cell antigen receptor. We searched for an antigen in the human environment that could induce T-cell recognition of this sequence. An analysis of protein and DNA databases revealed that the Epstein-Barr virus glycoprotein gp110, which is encoded by the BALF4 open reading frame, contains the sequence QKRAAQRAA, which is highly homologous to the rheumatoid arthritis susceptibility determinant. Experiments using antibodies to synthetic peptides showed that the QKRAA determinant is expressed on the gp110 protein. Humans with serologic evidence of Epstein-Barr virus infection had serum antibodies to gp110 and peripheral blood T cells that recognized peptides from gp110 and HLA-Dw4 encompassing the QKRAA determinant.
AuthorsJ Roudier, J Petersen, G H Rhodes, J Luka, D A Carson
JournalProceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 86 Issue 13 Pg. 5104-8 (Jul 1989) ISSN: 0027-8424 [Print] United States
PMID2472638 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Epitopes
  • Epstein-Barr virus glycoprotein gp110
  • HLA-D Antigens
  • HLA-Dw4 antigen
  • Immunoglobulin G
  • Immunoglobulin M
  • Macromolecular Substances
  • Viral Proteins
Topics
  • Amino Acid Sequence
  • Arthritis, Rheumatoid (genetics, immunology)
  • Enzyme-Linked Immunosorbent Assay
  • Epitopes (analysis)
  • HLA-D Antigens (genetics)
  • Humans
  • Immunoglobulin G (genetics)
  • Immunoglobulin M (genetics)
  • Macromolecular Substances
  • Molecular Sequence Data
  • T-Lymphocytes (immunology)
  • Viral Proteins (genetics)

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