Autoimmune rheumatologic diseases

Oral

Identification and Functional Characterization of T Cell Reactive to Citrullinated Tenascin-C in HLA-DRB1*0401-Positive Rheumatoid Arthritis Patients

Thursday, June 15
4:31 PM - 4:44 PM

Anti-citrullinated protein antibodies (ACPAs) are a hallmark of rheumatoid arthritis (RA) and target a number of synovial and inflammation associated proteins. Antibodies against Tenascin-C, an extracellular matrix protein, have been observed in ACPA+ RA patients and a citrullinated peptide was recently identified as their major target. Our aim was to determine whether T cell responses against cit-tenascin-C are present in subjects with RA. We utilized an algorithm to predict 64 possible HLA-DRB1*0401 restricted epitopes within tenascin-C based on its binding motif. These peptides were tested in a binding assay, identifying 10 citrullinated peptides that bound with moderate to high affinity. We next performed in vitro assays, expanding PBMC obtained from HLA-DRB1*0401+ patients and staining with HLA class II tetramers, confirming 6 of these peptides as immunogenic. We utilized tetramers to directly stain cit-tenascin-C specific T cells and observed that tenascin-C specific cells were readily visualized in the peripheral blood of HLA-DR*0401+ patients. To further investigate the specificity of tenascin-C specific T cells, we isolated a T cell clone from an RA patient using ex vivo single cell sorting. The expanded clone remained tetramer positive and proliferated in response to a citrullinated tenascin-C peptide (1012-1026 modified at amino acids 1014 and 1016). These results demonstrate that T cells that recognize citrullinated tenascin-C peptides are present in HLA–DRB1*0401+ RA patients. We expect that further characterization of cit-tenascin-C specific T cells will indicate unique functional characteristics and others that are shared by T cells that recognize conventional RA autoantigens

Jing Song

Postdoc
Benaroya Research Institute at Virginia Mason

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Cliff Rims

Research Tech III
Benaroya Research Institute

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Send Email for David Arribas-Layton

Send Email for Eddie James

Send Email for Jane Buckner


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Identification and Functional Characterization of T Cell Reactive to Citrullinated Tenascin-C in HLA-DRB1*0401-Positive Rheumatoid Arthritis Patients



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