A molecular basis of human T cell receptor autoreactivity toward self-phospholipids

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Science Immunology  20 Oct 2017:
Vol. 2, Issue 16, eaao1384
DOI: 10.1126/sciimmunol.aao1384

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Avoiding lipid autoreactivity

The importance of self-tolerance is appreciated in the context of presentation of peptide antigens to T cells. Much less is known about how lipid-reactive T cells avoid reacting to abundant self-lipids. Here, Shahine et al. studied an autoreactive T cell receptor (TCR) that recognizes a rare self-phospholipid, phosphatidylglycerol (PG). They solved the structure of this TCR bound to CD1b-PG complex and compared this with previously solved structures of CD1-lipid-TCR ternary complexes. The authors found that, in the context of CD1b, TCR binding to abundant self-phospholipids is usually sterically or electrostatically repelled, and propose that this facilitates avoidance of T cell autoreactivity to ubiquitous self-phospholipids.

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