p205 is a major target of autoreactive T cells in rheumatoid arthritis.
OBJECTIVE
The p205 autoantigen and interleukin-2 (IL-2) function synergistically to stimulate T lymphocytes from patients with rheumatoid arthritis (RA), and a p205-derived amino acid sequence is identical to an immunoglobulin sequence located within a domain that is reactive with rheumatoid factors (RF). This study was conducted to analyze in detail the T cell immune response against p205 and to investigate whether immunity to p205 may play a role in T cell-mediated immunopathology in active RA.


METHODS
Cibachron blue, protein A-Sepharose, and gel filtration on Sephacryl were used successively to enrich p205 from synovial fluid (SF). T lymphocytes from RA patients were isolated from the peripheral blood (PB), lymph nodes, and SF, and p205 and peptides derived from known sequences were assessed by T cell proliferation assays in the presence of IL-2.


RESULTS
P205-specific proliferation of T cells was observed in PB as well as in SF. When p205 was isolated from RA SF, proliferation of RA T cells peaked on day 3. With p205 purified from SF from trauma patients, there was a significant shift of the maximum T cell proliferation to day 8. T cells were of CD4 or CD8 phenotype, and B cells did not proliferate to a significant degree. The T cell response to p205 was always higher for SF mononuclear cells (SFMC) compared with PBMC (P < 0.001). In 1 RA patient who underwent repeated leukapheresis, this led to a reproducible decline in p205-specific T cell proliferation to control levels. PB T cells specifically proliferating in response to p205 were detected in 20 of 32 RA patients (63%). Of 26 patients with other inflammatory rheumatic diseases, only 1 showed a minor response to p205, while normal donors did not demonstrate a significant T cell proliferation. A synthetic p205-derived peptide, with an amino acid sequence identical to an immunoglobulin sequence located in the area where RF binds, was reactive with T cells from RA patients.


CONCLUSIONS
P205 appears to be a major target of autoreactive T cells in RA. P205-specific T cells are primed and more abundant at the site of inflammation. As a T cell target in RA, p205 may well be an antigen involved in the initiation of RF production.
D000328:Adult; D000938:Antigen-Presenting Cells / Q000502:physiology; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D001324:Autoantigens / Q000302:isolation & purification; D000939:Epitopes / Q000276:immunology; D005260:Female; D006680:HLA Antigens / Q000502:physiology; D006801:Humans; D007700:Kinetics; D007963:Leukocytes, Mononuclear / Q000502:physiology; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009479:Neuropeptides / Q000276:immunology*; D000075370:Receptors for Activated C Kinase; D012680:Sensitivity and Specificity; D013582:Synovial Fluid / Q000166:cytology; D013601:T-Lymphocytes / Q000276:immunology*