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Strength and Numbers: The Role of Affinity and Avidity in the ‘Quality’ of T Cell Tolerance

1
Centre de Recherche de l’Hôpital Maisonneuve-Rosemont, Montréal, QC H1T 2M4, Canada
2
Département de Microbiologie, Immunologie et Infectiologie, Université de Montréal, Montréal, QC H3C 3J7, Canada
3
Département de Médecine, Université de Montréal, Montréal, QC H3T 1J4, Canada
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Alessandro Poggi
Cells 2021, 10(6), 1530; https://doi.org/10.3390/cells10061530
Received: 31 May 2021 / Revised: 13 June 2021 / Accepted: 14 June 2021 / Published: 17 June 2021
(This article belongs to the Collection Feature Papers in Cellular Immunology)
The ability of T cells to identify foreign antigens and mount an efficient immune response while limiting activation upon recognition of self and self-associated peptides is critical. Multiple tolerance mechanisms work in concert to prevent the generation and activation of self-reactive T cells. T cell tolerance is tightly regulated, as defects in these processes can lead to devastating disease; a wide variety of autoimmune diseases and, more recently, adverse immune-related events associated with checkpoint blockade immunotherapy have been linked to a breakdown in T cell tolerance. The quantity and quality of antigen receptor signaling depend on a variety of parameters that include T cell receptor affinity and avidity for peptide. Autoreactive T cell fate choices (e.g., deletion, anergy, regulatory T cell development) are highly dependent on the strength of T cell receptor interactions with self-peptide. However, less is known about how differences in the strength of T cell receptor signaling during differentiation influences the ‘function’ and persistence of anergic and regulatory T cell populations. Here, we review the literature on this subject and discuss the clinical implications of how T cell receptor signal strength influences the ‘quality’ of anergic and regulatory T cell populations. View Full-Text
Keywords: T cells; tolerance; T cell receptor signaling; affinity; avidity; anergy; regulatory T cells (Treg); heterogeneity; immunotherapy T cells; tolerance; T cell receptor signaling; affinity; avidity; anergy; regulatory T cells (Treg); heterogeneity; immunotherapy
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MDPI and ACS Style

This, S.; Valbon, S.F.; Lebel, M.-È.; Melichar, H.J. Strength and Numbers: The Role of Affinity and Avidity in the ‘Quality’ of T Cell Tolerance. Cells 2021, 10, 1530. https://doi.org/10.3390/cells10061530

AMA Style

This S, Valbon SF, Lebel M-È, Melichar HJ. Strength and Numbers: The Role of Affinity and Avidity in the ‘Quality’ of T Cell Tolerance. Cells. 2021; 10(6):1530. https://doi.org/10.3390/cells10061530

Chicago/Turabian Style

This, Sébastien, Stefanie F. Valbon, Marie-Ève Lebel, and Heather J. Melichar. 2021. "Strength and Numbers: The Role of Affinity and Avidity in the ‘Quality’ of T Cell Tolerance" Cells 10, no. 6: 1530. https://doi.org/10.3390/cells10061530

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