Diversity in antigen recognition by Mycobacterium tuberculosis‐reactive T cell clones from the synovial fluid of rheumatoid arthritis patients

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Abstract
In a previous study we have shown that synovial fluid mononuclear cells from many rheumatoid arthritis (RA) patients exhibit an enhanced response to M. tuberculosis antigens as compared to peripheral blood mononuclear cells. The 65‐kDa heat‐shock protein of M. tuberculosis was shown not to play an important role in this response, therefore other mycobacterial proteins must be involved. In this study we have investigated the possibility that synovial fluid T cells from RA patients predominantly recognize a limited number of M. tuberculosis antigens, as a result of a lesion‐specific activation of only those M. tuberculosis‐reactive T cells that have cross‐reacted with joint‐related autoantigens. From the synovial fluid of four RA patients M. tuberculosis‐reactive T cell clones were isolated and analyzed for their phenotype, HLA‐DR restriction and proliferation to immunoblot fractions containing sodium dodecyl sulfate‐polyacrylamide gel‐separated M. tuberculosis proteins of known molecular weight range. The overall M. tuberculosis immunoblot recognition pattern of the clones was strikingly heterogeneous. Within a panel of 15 clones 12 different antigenic specificities could be distinguished. In other words, we did not observe a dominant recognition of a few M. tuberculosis antigens by synovial fluid T cells. This argues against the hypothesis that the elevated synovial T cell reactivity against M. tuberculosis is a reflection of an in vivo expansion of a limited number of different types of M. tuberculosis‐reactive T cells as a result of a cross‐reaction with putative joint autoantigens.