An autoimmune TCR (left; red and yellow) sits off-center on its MHC (blue) and peptide (green) compared with a more conventional arrangement (right).

WUCHERPFENNIG/MACMILLAN

A crooked T cell receptor (TCR)–MHC interaction may result in immune responses that are similarly skewed, based on findings from Michael Hahn, Kai Wucherpfennig, and colleagues (Dana-Farber Cancer Institute, Boston, MA). The TCR in question is associated with multiple sclerosis, suggesting that protective and autoimmune T cells recognize antigens differently.

A head-on approach has been seen in protective cases, in which the TCR sits directly atop the foreign peptide/MHC complex on an antigen-presenting cell. Now, the authors present the first crystal structure of an autoimmunity-generating complex—a TCR that binds to MHC presenting the myelin basic protein (MBP) peptide.

This structure, derived from a TCR that was isolated from a multiple sclerosis patient, reveals a tilted complex in which the TCR contacted...

The Rockefeller University Press
2005
The Rockefeller University Press
2005
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