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Unconventional T-cell recognition of an arthritogenic epitope of proteoglycan aggrecan released from degrading cartilage

Lookup NU author(s): Dr Jane Falconer, Dr Rahul Mahida, Divya Venkatesh, Professor Jeffrey Pearson, Emeritus Professor John Robinson



This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0).


It has been proposed that peptide epitopes bind to MHC class II molecules to form distinct structural conformers of the same MHC II-peptide complex termed type A and type B, and that the two conformers of the same peptide-MHC II complex are recognized by distinct CD4 T cells, termed type A and type B T cells. Both types recognize short synthetic peptides but only type A recognize endosomally processed intact antigen. Type B T cells that recognize self peptides from exogenously degraded proteins have been shown to escape negative selection during thymic development and so have the potential to contribute to the pathogenesis of autoimmunity. We generated and characterized mouse CD4 T cells specific for an arthritogenic epitope of the candidate joint autoantigen proteoglycan aggrecan. Cloned T-cell hybridomas specific for a synthetic peptide containing the aggrecan epitope showed two distinct response patterns based on whether they could recognize processed intact aggrecan. Fine mapping demonstrated that both types of T-cell recognized the same core epitope. The results are consistent with the generation of aggrecan-specific type A and type B T cells. Type B T cells were activated by supernatants released from degrading cartilage, indicating the presence of antigenic extracellular peptides or fragments of aggrecan. Type B T cells could play a role in the pathogenesis of proteoglycan-induced arthritis in mice, a model for rheumatoid arthritis, by recognizing extracellular peptides or protein fragments of joint autoantigens released by inflamed cartilage.

Publication metadata

Author(s): Falconer J, Mahida R, Venkatesh D, Pearson J, Robinson JH

Publication type: Article

Publication status: Published

Journal: Immunology

Year: 2016

Volume: 147

Issue: 4

Pages: 389-398

Print publication date: 01/04/2016

Online publication date: 18/11/2015

Acceptance date: 06/11/2015

Date deposited: 20/06/2016

ISSN (print): 0019-2805

ISSN (electronic): 1365-2567

Publisher: Wiley-Blackwell Publishing, Inc.


DOI: 10.1111/imm.12557


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