Evidence for the effects of a superantigen in rheumatoid arthritis.
While studying the alpha beta T cell receptor repertoire in rheumatoid arthritis (RA) patients, we found that the frequency of V beta 14+ T cells was significantly higher in the synovial fluid of affected joints than in the peripheral blood. In fact, V beta 14+ T cells were virtually undetectable in the peripheral blood of a majority of these RA patients. beta-chain sequences indicated that one or a few clones dominated the V beta 14+ population in the synovial fluid of individual RA patients, whereas oligoclonality was less marked for other V beta's and for V beta 14 in other types of inflammatory arthritis. These results implicate V beta 14-bearing T cells in the pathology of RA. They also suggest that the etiology of RA may involve initial activation of V beta 14+ T cells by a V beta 14-specific superantigen with subsequent recruitment of a few activated autoreactive v beta 14+ T cell clones to the joints while the majority of other V beta 14+ T cells disappear.
Paliard
X
X
Howard Hughes Medical Institute, Denver, CO.
West
S G
SG
Lafferty
J A
JA
Clements
J R
JR
Kappler
J W
JW
Marrack
P
P
Kotzin
B L
BL
D000595:Amino Acid Sequence; D001168:Arthritis / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000276:immunology*; D006681:HLA-D Antigens / Q000032:analysis*; D006801:Humans; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D011948:Receptors, Antigen, T-Cell / Q000032:analysis*; D013582:Synovial Fluid / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D006681:HLA-D Antigens; D046911:Macromolecular Substances; D011948:Receptors, Antigen, T-Cell