Date: Monday, November 9, 2015
Session Title: T cell Biology and Targets in Autoimmune Disease Poster I
Session Type: ACR Poster Session B
Session Time: 9:00AM-11:00AM
Antibodies against citrullinated collagen type II (Cit-CII) are common in sera and synovial fluids of Rheumatoid Arthritis (RA) patients, whereas the known CII T-cell epitope is not dependent on citrullination. This study aimed to identify Cit-CII restricted T-cell epitopes relevant to RA and to functionally characterize Cit-CII specific CD4+ T cells with regard to immune function and TCR Vbeta signatures.
Methods: PBMCs from HLA-DRB1*10:01 positive RA patients and healthy donors were stimulated with candidate peptides in vitro. CD154 up-regulation was utilized as a marker of antigen-specific activation. One citrullinated peptide, Cit-CII(311-325) was able to activate CD4+ T cells and was selected for further analysis. Cytokine production measurement by Luminex technology and anti-DR blocking experiments were conducted. Direct binding assays using HLA-DRB1*10:01 and *04:01 monomers were performed. Antigen-specific T cells were CD154-enriched and their T-Cell Receptor (TCR) Vbeta chain was sequenced with high-throughput sequencing.
A new citrullinated CII peptide was identified based on its ability to activate CD4+ T cells from HLA-DRB1*10:01individuals. When stimulated in vitro, Cit-CII autoreactive T cells produced pro-inflammatory cytokines. Cit-CII(311-325) binds with low affinity to HLA-DRB1*10:01 but not to HLA-DRB1*0401 while the native version was unable to bind either of them. Finally, Highly Expanded Clones (HECs) were identified in the TCR Vbeta repertoire of Cit-CII(311-325) stimulated PBMCs.
These results illustrate the ability of the citrullination process to create T-cell epitopes from CII, a cartilage-restricted protein relevant to RA pathogenesis. The exclusive binding of Cit-CII(311-325) to HLA*DRB1*10:01 suggests that citrulline T-cell autoimmunity might vary between individuals carrying different RA-associated HLA-DR molecules.
To cite this abstract in AMA style:Chemin K, Pollastro S, James E, Ge C, Albrecht I, Herrath J, Gerstner C, Rizzi T, Tandre K, Rönnblom L, Catrina AI, Holmdahl R, Klareskog L, De Vries N, Malmström V. A Novel HLA-DRB1*10:01 Restricted T Cell Epitope from Citrullinated Type II Collagen Relevant for Rheumatoid Arthritis [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/a-novel-hla-drb11001-restricted-t-cell-epitope-from-citrullinated-type-ii-collagen-relevant-for-rheumatoid-arthritis/. Accessed January 20, 2020.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/a-novel-hla-drb11001-restricted-t-cell-epitope-from-citrullinated-type-ii-collagen-relevant-for-rheumatoid-arthritis/