Detection of T cell responses to a ubiquitous cellular protein in autoimmune disease

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Science  17 Oct 2014:
Vol. 346, Issue 6207, pp. 363-368
DOI: 10.1126/science.1259077

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T cells that mediate autoimmune diseases such as rheumatoid arthritis (RA) are difficult to characterize because they are likely to be deleted or inactivated in the thymus if the self antigens they recognize are ubiquitously expressed. One way to obtain and analyze these autoimmune T cells is to alter T cell receptor (TCR) signaling in developing T cells to change their sensitivity to thymic negative selection, thereby allowing their thymic production. From mice thus engineered to generate T cells mediating autoimmune arthritis, we isolated arthritogenic TCRs and characterized the self antigens they recognized. One of them was the ubiquitously expressed 60S ribosomal protein L23a (RPL23A), with which T cells and autoantibodies from RA patients reacted. This strategy may improve our understanding of the underlying drivers of autoimmunity.

Finding the targets of T cells gone bad

Autoimmune diseases such as rheumatoid arthritis can result when the immune system attacks its own body. If we could identify the specific proteins targeted by autoimmune T cells, we might then be able to block this interaction, which might be useful therapeutically. Ito et al. identified one such target in mice that develop a disease similar to rheumatoid arthritis. Disease-causing T cells recognized a protein that is part of the ribosome, a large protein complex that catalyzes protein synthesis. They also found T cells specific for this protein in people with rheumatoid arthritis.

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