On T cell development, T cell signals, T cell specificity and sensitivity, and the autoimmunity facilitated by lymphopenia

© 2020 The Scandinavian Foundation for Immunology..

We propose a framework to explain how T cells achieve specificity and sensitivity, how the affinity of the TcR peptide/MHC interaction controls positive and negative thymic selection and mature T cell survival, and whether antigen-dependent activation and inactivation takes place. Two distinct types of signalling can lead to mature T cell multiplication. One requires the TcR to recognize with a certain affinity an antigen-derived peptide, an agonist peptide, bound to an MHC molecule. The other, the tonic signal, leads to naïve T cell survival and modest proliferation if the T cell successfully competes for endogenous, self-peptide/MHC ligands, involving lower affinity TCR/ligand interactions. Many suggest lymphopenia contributes to autoimmunity by increasing the strength of TcR-tonic signalling, and so activation of anti-self T cells. We suggest T cell activation requires antigen-mediated cooperation between T cells. Increased tonic signalling under lymphopenic conditions facilitates T cell proliferation and so antigen-dependent cooperation and activation of anti-self T cells.

Medienart:

E-Artikel

Erscheinungsjahr:

2020

Erschienen:

2020

Enthalten in:

Zur Gesamtaufnahme - volume:91

Enthalten in:

Scandinavian journal of immunology - 91(2020), 6 vom: 24. Juni, Seite e12888

Sprache:

Englisch

Beteiligte Personen:

Bretscher, Peter A [VerfasserIn]
Al-Yassin, Ghassan [VerfasserIn]
Anderson, Colin C [VerfasserIn]

Links:

Volltext

Themen:

Autoantigens
Borderline peptides
CD5
Histocompatibility Antigens
Journal Article
Lymphopenia-induced proliferation
Negative selection
Peptide Fragments
Peripheral autoimmunity
Positive selection
Principle of parsimonious sensitivity
Promiscuous T cells
Receptors, Antigen, T-Cell
Signal 1 for T cells
Tonic signalling

Anmerkungen:

Date Completed 08.06.2020

Date Revised 08.06.2020

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1111/sji.12888

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM308667352