Non-Antigenic Modulation of Antigen Receptor (TCR) Cβ-FG Loop Modulates Signalling: Implications of External Factors Influencing T-Cell Responses

Author:

Manolios Nicholas12ORCID,Pham Son3ORCID,Hou Guojiang2ORCID,Du Jonathan4ORCID,Quek Camelia3,Hibbs David4ORCID

Affiliation:

1. Faculty of Medicine and Health, The University of Sydney, Sydney, NSW 2006, Australia

2. Department of Rheumatology, Westmead Hospital, Sydney, NSW 2145, Australia

3. Sydney Medical School, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW 2006, Australia

4. The University of Sydney School of Pharmacy, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW 2006, Australia

Abstract

T-cell recognition of antigens is complex, leading to biochemical and cellular events that impart both specific and targeted immune responses. The end result is an array of cytokines that facilitate the direction and intensity of the immune reaction—such as T-cell proliferation, differentiation, macrophage activation, and B-cell isotype switching—all of which may be necessary and appropriate to eliminate the antigen and induce adaptive immunity. Using in silico docking to identify small molecules that putatively bind to the T-cell Cβ-FG loop, we have shown in vitro using an antigen presentation assay that T-cell signalling is altered. The idea of modulating T-cell signalling independently of antigens by directly targeting the FG loop is novel and warrants further study.

Publisher

MDPI AG

Subject

Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis

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