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The discriminatory power of the T cell receptor.

ABSTRACT: T cells use their T cell receptors (TCRs) to discriminate between lower-affinity self and higher-affinity non-self peptides presented on major histocompatibility complex (pMHC) antigens. Although the discriminatory power of the TCR is widely believed to be near-perfect, technical difficulties have hampered efforts to precisely quantify it. Here, we describe a method for measuring very low TCR/pMHC affinities and use it to measure the discriminatory power of the TCR and the factors affecting it. We find that TCR discrimination, although enhanced compared with conventional cell-surface receptors, is imperfect: primary human T cells can respond to pMHC with affinities as low as K_D ∼ 1 mM. The kinetic proofreading mechanism fit our data, providing the first estimates of both the time delay (2.8 s) and number of biochemical steps (2.67) that are consistent with the extraordinary sensitivity of antigen recognition. Our findings explain why self pMHC frequently induce autoimmune diseases and anti-tumour responses, and suggest ways to modify TCR discrimination.

SUBMITTER: Pettmann J

PROVIDER: S-EPMC8219380 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature

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The discriminatory power of the T cell receptor.

Pettmann Johannes J Huhn Anna A Abu Shah Enas E Kutuzov Mikhail A MA Wilson Daniel B DB Dustin Michael L ML Davis Simon J SJ van der Merwe P Anton PA Dushek Omer O

eLife 20210525

T cells use their T cell receptors (TCRs) to discriminate between lower-affinity self and higher-affinity non-self peptides presented on major histocompatibility complex (pMHC) antigens. Although the discriminatory power of the TCR is widely believed to be near-perfect, technical difficulties have hampered efforts to precisely quantify it. Here, we describe a method for measuring very low TCR/pMHC affinities and use it to measure the discriminatory power of the TCR and the factors affecting it. ...[more]

PMID: 34030769

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The discriminatory power of the T cell receptor.

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The discriminatory power of the T cell receptor.

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