The discriminatory power of the T cell receptor.
Elife
; 102021 05 25.
Article
em En
| MEDLINE
| ID: mdl-34030769
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 KD â¼ 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.
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Base de dados:
MEDLINE
Assunto principal:
Peptídeos
/
Receptores de Antígenos de Linfócitos T
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article