Detection of T cell responses to a ubiquitous cellular protein in autoimmune disease
Science, 2014•science.org
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 …
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 …
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.
AAAS