There is abundant evidence to implicate an immune response to Type II collagen in the pathogenesis of rheumatoid arthritis. We hypothesize that cell-mediated immunity to Type II collagen may be important in the self-perpetuation of rheumatoid synovitis. Further we hypothesize that the mechanism by which T cells from patients with rheumatoid arthritis recognize Type II collagen may be important in the pathogenesis of rheumatoid arthritis. Therefore, we propose to isolate T cells from rheumatoid synovial fluid and tissue which recognize Type II collagen in an antigen specific fashion. Similar lymphocytes will be isolated from rheumatoid and normal peripheral blood if possible. We propose to clone these T lymphocytes by limiting dilution. The specificity of and restriction elements responsible for presentation of antigen to these T cells will be determined as will the antigen specificity of the clones generated. Three to 6 clones from the synovial fluid or tissue of patients will be employed to characterize the T cell receptors involved in the specific recognition of collagen. To perform these studies polyadenylated mRNA will be isolated from the T cell clones and a cDNA library will be constructed to isolate and characterize productively rearranged transcripts. Those colonies containing the T cell receptor B- chain genes will be expanded and isolated. The VB regions will be sequenced using the Dideoxy method. The determined sequences will be alligned with known sequences and similarity between antigen specific and nonspecific clones will be determined. These studies may provide new insights into the pathogenesis of rheumatoid arthritis and may suggest new therapeutic strategies for its treatment.

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Northwestern University at Chicago
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