Recognition of a mycobacteria-specific epitope in the 65-kD heat-shock protein by synovial fluid-derived T cell clones.
Adjuvant arthritis in rats is induced by a T cell clone specific for amino acids 180-188 of the mycobacterial 65-kD heat-shock protein, and synovial T cell responses to this same Ag have been noted in human arthritis. We have isolated 65-kD Ag-specific T cell clones from synovial fluid mononuclear cells of a patient with acute arthritis, which, unlike the corresponding PBMC, showed a marked proliferative response to the 65-kD Ag. Using synthetic peptides corresponding to the whole sequence of the 65-kD Ag, all the clones were shown to recognize an epitope present in the first NH2-terminal peptide (amino acids 1-15), with no response to the adjacent peptide (amino acids 6-22) or to any other peptide. The complete dominance of this epitope in the response to the 65-kD Ag was shown by documenting responses to the peptide in PBMC obtained after recovery from the arthritis. This epitope, like that recognized by the rat arthritogenic T cell clone, is in a portion of the 65-kD sequence that is not conserved between bacteria and eukaryotes, so that in this case, joint inflammation could not be attributed to bacteria-induced T cell clones cross-reacting with the self 65-kD Ag.
Department of Rheumatology, University of Birmingham, United Kingdom.
J S
JS
Gaston
P F
PF
Life
P J
PJ
Jenner
M J
MJ
Colston
P A
PA
Bacon
D000942:Antigens, Bacterial / Q000276:immunology*; D002999:Clone Cells; D000939:Epitopes / Q000032:analysis*; D006684:HLA-DR Antigens / Q000032:analysis; D006360:Heat-Shock Proteins / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D009161:Mycobacterium / Q000276:immunology*; D013582:Synovial Fluid / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D000942:Antigens, Bacterial; D000939:Epitopes; D006684:HLA-DR Antigens; D006360:Heat-Shock Proteins