Key words: EBV gp110; HLA-DRB1; rheumatoid arthritis; T cell Acknowledgments: This work was supported by grants from INSERM, Association pour la Recherche sur la Polyarthrite, Socie ´te ´ Franc ¸aise de Rhumatologie, and PHRC 1994, 1996, 1997. We thank J.F. Eliaou and J. Clot (Montpellier) and L. Geburher (Lyon) for providing typed controls. Received 13 January, revised, accepted for publication 25 May 1999 Copyright c Munksgaard 1999 Tissue Antigens . ISSN 0001-2815 Tissue Antigens 1999: 54: 146–152 Printed in Denmark . All rights reserved 146 E. Toussirot HLA-DR polymorphism influences T-cell I. Auger precursor frequencies to Epstein-Barr virus C. Roudier J. Luka (EBV) gp110: implications for the D. Wendling P. Tiberghien association of HLA-DR antigens with J. Roudier rheumatoid arthritis Abstract: To study whether HLA-DR haplotypes associated with suscepti- bility to develop rheumatoid arthritis (RA) may influence T-cell responses to the Epstein-Barr virus (EBV) gp110 (a protein of the late replicative cycle of EBV), we evaluated the frequency in peripheral blood of T cells capable to pro- liferate to EBV gp110 by direct limiting dilution analysis in 50 HLA-DR-typ- ed healthy subjects. We found that HLA-DRB1*07, an allele associated with reduced risk to develop RA, is associated with the highest frequencies of T cells specific for gp110 in peripheral blood. In contrast, HLA-DRB1*0404, one of the susceptibility alleles is associated with the lowest frequencies of gp110 specific T cells. Finally, people expressing both HLA-DRB1*07 and HLA- DRB1*0404 display low precursor frequencies to EBV gp110. Most patients with rheumatoid arthritis, a chronic inflammatory joint disease, express particular HLA-DR alleles whose DRb1 chains share a highly conserved amino acid motif called the shared epitope (1). The most common shared epitope-positive alleles in Western Europe are HLA-DRB1*0401, DRB1*0404, DRB1*0405, DRB1*0408, DRB1*0101, DRB1*0102 and DRB1*1001. The mechanisms by which shared epitope-positive HLA-DR alleles help the development of rheumatoid arthritis (RA) are still unknown. In this study, we tested the hypothesis that they may influence the status of Epstein- Barr virus (EBV) infection. Indeed, in patients with RA, the percen- tage of EBV-infected peripheral blood B lymphocytes is higher than in controls (2) and EBV DNA is detected in the saliva or peripheral blood more often than in controls (3). These observations suggest that RA is associated with EBV overload. Defective control of EBV replication in RA patients has never been correlated with the HLA- DR background on which disease develops. In this study, we tested whether the HLA-DR background which predisposes to develop RA may influence T-cell responses to a late antigen of the EBV replicative cycle which is the main component of the VCA antigen: gp110 (4). Authors’ affiliations: E. Toussirot 1 , I. Auger 4 , C. Roudier 4 , J. Luka 3 , D. Wendling 1 , P. Tiberghien 2 , J. Roudier 4 1 Service de Rhumatologie, Hopital Minjoz, Besanc ¸on, France, 2 Etablissement de Transfusion Sanguine, Besanc ¸on, France, 3 Eastern Virginia Medical School, Department of Pathology, Norfolk, Virginia, USA, 4 Laboratoire d’Immuno Rhumatologie, INSERM E9940, Faculte ´ de Me ´decine de Marseille, Marseille, France Correspondence to: Jean Roudier Laboratoire d’Immuno Rhumatologie INSERM E9940 Faculte ´ de Me ´decine 13005 Marseille France Tel: π33 491 32 44 97 Fax: π33 491 83 09 26 e-mail: roudier/aix.pacwan.net