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Recognition of self-peptide-MHC complexes by autoimmune T-cell receptors.

ABSTRACT: T cell receptors (TCR) recognize antigenic peptides displayed by MHC molecules. Whereas T-cell recognition of foreign peptides is essential for immune defense against microbial pathogens, recognition of self-peptides can cause autoimmune disease. Structural studies of anti-foreign TCR showed remarkable similarities in the topology of TCR binding to peptide-MHC, which maximize interactions with the ligand. However, recent structures involving autoimmune and tumor-specific TCR have revealed that they engage self-peptide-MHC with different topologies, which are suboptimal for TCR binding. These differences might reflect the distinct selection pressures exerted on anti-microbial versus autoreactive T cells. The structures also provide new insights into TCR cross-reactivity, which can contribute to autoimmunity by increasing the likelihood of self-peptide-MHC recognition.

SUBMITTER: Deng L

PROVIDER: S-EPMC2739108 | biostudies-literature | 2007 Nov

REPOSITORIES: biostudies-literature

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Recognition of self-peptide-MHC complexes by autoimmune T-cell receptors.

Deng Lu L Mariuzza Roy A RA

Trends in biochemical sciences 20071022 11

T cell receptors (TCR) recognize antigenic peptides displayed by MHC molecules. Whereas T-cell recognition of foreign peptides is essential for immune defense against microbial pathogens, recognition of self-peptides can cause autoimmune disease. Structural studies of anti-foreign TCR showed remarkable similarities in the topology of TCR binding to peptide-MHC, which maximize interactions with the ligand. However, recent structures involving autoimmune and tumor-specific TCR have revealed that t ...[more]

PMID: 17950605

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