Cambridge                    Edwards Sympositum                September 12, 2025

Specificity and tolerance of the immune T cell repertoire

Arup K. Chakraborty 

 

Andrej Kosmrlj,   Hanrong Chen,   Tom Butler,  Eric Huseby,   Sam Melton ,     Rose Yin    

Outline

I.      The adaptive immune system: T cells, antigen presentation, specificity and tolerance                                       

II.      Thymic Selection: positive and negative selection, specificity from weak amino-acids, extreme value distribution

III.     Quorum Sensing for peripheral tolerance

IV.     Persistent infections and onset of autoimmunity

V.      Summary

 

 

 

 

Title: 
Specificity and tolerance of the immune T cell repertoire

Abstract:  
The adaptive immune system protects the body from an ever-changing landscape of foreign pathogens. The two arms of the adaptive immune system, T cells and B cells, mount specific responses to pathogens by utilizing the diversity of their receptors, generated through hypermutation. T cells recognize and clear infected hosts when their highly variable receptors bind sufficiently strongly to antigen-derived peptides displayed on a cell surface. To avoid auto-immune responses, randomly generated receptors that bind strongly to self-peptides are eliminated in the “central" process of thymic selection, ensuring a mostly self-tolerant repertoire of mature T cells. “Peripheral” tolerance, including a quorum mechanism further protects against self-targeting T cells that escape thymic selection. We discuss how these mechanisms can still fail during persistent infections.