Susceptibility to Rheumatoid Arthritis Maps to a T-Cell Epitope Shared by the HLA-Dw4 DR β -1 Chain and the Epstein-Barr Virus Glycoprotein gp110

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 β -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.