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. 1997 May;56(5):317–322. doi: 10.1136/ard.56.5.317

Rheumatoid arthritis: autoreactive T cells recognising a novel 68k autoantigen

S Bla{beta} 1, C Haferkamp 1, C Specker 1, M Schwochau 1, M Schneider 1, E Schneider 1
PMCID: PMC1752372  PMID: 9175933

Abstract

OBJECTIVE—A 68k autoantigen has been identified by specific antibodies from patients with rheumatoid arthritis (RA). This study considered whether or not this antigen is a target for T cells and thus may play a part in T cell mediated immunopathology of active RA.
METHODS—The 68k antigen was isolated and used in a nitrocellulose bound form to stimulate T cells. Proliferation of T lymphocytes of peripheral blood as well as synovial fluid was measured.
RESULTS—Peripheral blood T cells specifically proliferating against the 68k antigen were detected in 19 of 27 patients with RA (70%). For T cells isolated from peripheral blood, proliferation peaked on day 10. When T cells were isolated from actively inflamed synovial fluid, the proliferation kinetics shifted to a peak on day 3. Blockade of HLA class II antigens resulted in an increase of proliferation in the case of HLA-DP. Applying HLA-DP specific antibodies capable of inhibiting antigen presentation mediated by this molecule, T cells of 17 of 27 RA patients (63%) proliferated to a higher extent than with the 68k antigen alone. The phenomenon that an increased proliferation occurred upon blockade of a particular HLA class II family member was also demonstrated for DQ and DR: the 68k antigen likewise stimulated T cells restricted for DP or DQ, respectively.
CONCLUSIONS—The novel 68k antigen is a target of both T and B cellular immune responses and as such could play a part in the immune dysfunction of RA. The finding that blocking of certain HLA class II molecules functioning in antigen presentation (for example, via HLA-DQ) results in a higher instead of lower proliferation in vitro, may argue for the presence of antigen specific suppressive T cells.



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Figure 1  .

Figure 1  

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(A) Kinetic analysis of the proliferative response against the 68k antigen by PBMCs. Upper panel: proliferation upon stimulation with the 68k antigen peaking on day 10. PBMCs from RA patients 1-4. Lower panel: proliferation upon stimulation with the 64k control antigen peaking around day 5. PBMCs from RA patients 1-4 and a healthy control 5. (B) Kinetic analysis of the proliferative response against the 68k antigen by SFMCs. Upper panel: proliferation upon stimulation with the 68k antigen peaking on day 3 or 10. SFMCs from RA patients 1-4. Lower panel: proliferation upon stimulation with the 64k control antigen peaking around day 5. SFMCs from RA patients 1-4. 

Figure 2  .

Figure 2  

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T cell proliferation upon stimulation with the 68k antigen. In 19 of 27 RA patients (70%) 68k specific T cells could be detected. Proliferation with PBMCs of healthy controls has been set as 100%. Stimulation is considered to be positive for values greater than 120% (p < 0.0001).

Figure 3  .

Figure 3  

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(A) Increased 68k specific proliferation in the presence of anti-DP antibodies. Proliferation against the 68k antigen in the presence (DP) of a monoclonal antibody directed against HLA-DP is depicted for 27 RA patients. Seventeen of 27 RA patients (63%) present with an increased 68k specific proliferation when the HLA-DP antibody was added (proliferation in the presence of anti-DP antibodies + 68k antigen minus proliferation in the presence of the 68k antigen alone). (B) Increased 68k specific proliferation in the presence of anti-DQ antibodies. Proliferation against the 68k antigen in the presence (DQ) of a monoclonal antibody directed against HLA-DQ is depicted for 27 RA patients. Ten of 27 RA patients (37%) present with an increased 68k specific proliferation when the HLA-DQ antibody was added (proliferation in the presence of anti-DQ antibodies + 68k antigen minus proliferation in the presence of the 68k-antigen alone). (C) Increased 68k specific proliferation in the presence of anti-DR antibodies. Proliferation against the 68k antigen in the presence (DR) of a monoclonal antibody directed against HLA-DR is depicted for 27 RA patients. Thirteen of 27 RA patients (48%) present with an increased 68k specific proliferation when the HLA-DR antibody was added (proliferation in the presence of anti-DR antibodies + 68k antigen minus proliferation in the presence of the 68k antigen alone).

Selected References

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