Why does age matter? A structural analysis of T-cell receptors in young and elderly individuals

Presenter Information

Austin SeamannFollow

Advisor Information

Dario Ghersi

Presentation Type

Poster

Start Date

26-3-2021 12:00 AM

End Date

26-3-2021 12:00 AM

Abstract

Aging comes with a progressive decline in function of all organ systems and can affect the level of health that a person can achieve. A well-known example of this is provided by the immune system, which can be less prepared to fight off infection as people age. T-cells are critical to the function of an adaptive immune system. When a pathogen enters the body, a corresponding T-cell receptor (TCR) binds and constructs a response, eliminating instances of the pathogen throughout the body. TCRs are the recognition factor for Major Histocompatibility Complex bound peptides, found on nucleated cells, utilized to detect pathogens. The TCR structure can be predicted from sequence with modeling pipelines. An analysis was performed to determine a reliable modeling pipeline to be utilized. Modeled TCR structures of young adults and elderly individuals are compared in their ability to bind to antigen. Young adults show a larger repertoire of TCRs due to a more active thymus, the organ at which T-cells mature. In elderly, T-cells trade off binding affinity for broader recognition as their numbers dwindle. A comparison of young adult versus elderly TCRs was conducted to see structural factors for the shift in binding affinity.

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Mar 26th, 12:00 AM Mar 26th, 12:00 AM

Why does age matter? A structural analysis of T-cell receptors in young and elderly individuals

Aging comes with a progressive decline in function of all organ systems and can affect the level of health that a person can achieve. A well-known example of this is provided by the immune system, which can be less prepared to fight off infection as people age. T-cells are critical to the function of an adaptive immune system. When a pathogen enters the body, a corresponding T-cell receptor (TCR) binds and constructs a response, eliminating instances of the pathogen throughout the body. TCRs are the recognition factor for Major Histocompatibility Complex bound peptides, found on nucleated cells, utilized to detect pathogens. The TCR structure can be predicted from sequence with modeling pipelines. An analysis was performed to determine a reliable modeling pipeline to be utilized. Modeled TCR structures of young adults and elderly individuals are compared in their ability to bind to antigen. Young adults show a larger repertoire of TCRs due to a more active thymus, the organ at which T-cells mature. In elderly, T-cells trade off binding affinity for broader recognition as their numbers dwindle. A comparison of young adult versus elderly TCRs was conducted to see structural factors for the shift in binding affinity.