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- Title
The discriminatory power of the T cell receptor.
- Authors
Pettmann, Johannes; Huhn, Anna; Shah, Enas Abu; Kutuzov, Mikhail A.; Wilson, Daniel B.; Dustin, Michael L.; Davis, Simon J.; van der Merwe, P. Anton; Dushek, Omer
- Abstract
T cells use their T cell receptors (TCRs) to discriminate between lower-affnity self and higher- affnity 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 diffculties have hampered efforts to precisely quantify it. Here, we describe a method for measuring very low TCR/pMHC affnities and use it to measure the discriminatory power of the TCR and the factors affecting it. We fnd that TCR discrimination, although enhanced compared with conventional cell- surface receptors, is imperfect: primary human T cells can respond to pMHC with affnities as low as KD ~ 1 mM. The kinetic proofreading mechanism ft our data, providing the frst 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 fndings explain why self pMHC frequently induce autoimmune diseases and anti- tumour responses, and suggest ways to modify TCR discrimination.
- Subjects
T cell receptors; MAJOR histocompatibility complex; IMMUNE recognition; T cells; AUTOIMMUNE diseases
- Publication
eLife, 2021, p1
- ISSN
2050-084X
- Publication type
Article
- DOI
10.7554/eLife.67092