ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 1946

A Novel HLA-DRB1*10:01 Restricted T Cell Epitope from Citrullinated Type II Collagen Relevant for Rheumatoid Arthritis

Karine Chemin1, Sabrina Pollastro2, Eddie James3, Changrong Ge4, Inka Albrecht5, Jessica Herrath6, Christina Gerstner7, Thais Rizzi2, Karolina Tandre8, Lars Rönnblom8, Anca I Catrina9, Rikard Holmdahl10, L. Klareskog11, Niek De Vries12 and Vivianne Malmström11, 1Medicine, Rheumatology Unit, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden, 2Department of Clinical Immunology and Rheumatology, Amsterdam, Netherlands, 3Benaroya Research Institute at Virginia Mason, Seattle, WA, 4Department of Medical Biochemistry and Biophysics, Medical Inflammation Research, Karolinska Institute, Stockholm, Sweden, 5Rheumatology Unit, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden, 6Department of Medicine,, Rheumatology Unit, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden, 7Department of Medicine, Rheumatology Unit, Karolinska University Hospital, Solna, Stockholm, Sweden, 8Section of Rheumatology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden, 9Unit of Rheumatology, Department of Medicine Solna, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden, 10Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden, 11Rheumatology Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden, 12Dept. of Clinical Immunology & Rheumatology, Amsterdam Rheumatology and immunology Center, Academic Medical Center/University of Amsterdam, Amsterdam, Netherlands

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: , , ,

Session Information

Date: Monday, November 9, 2015

Title: T cell Biology and Targets in Autoimmune Disease Poster I

Session Type: ACR Poster Session B

Session Time: 9:00AM-11:00AM

Background/Purpose:

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.

Results:

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.

Conclusion:

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.

Disclosure: K. Chemin, None; S. Pollastro, None; E. James, None; C. Ge, None; I. Albrecht, None; J. Herrath, None; C. Gerstner, None; T. Rizzi, None; K. Tandre, None; L. Rönnblom, None; A. I. Catrina, None; R. Holmdahl, None; L. Klareskog, None; N. De Vries, None; V. Malmström, None.

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 .

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