The influence of T cell development on pathogen specificity and autoreactivity

TL;DR

This paper models how thymic selection influences T cell receptor diversity, balancing pathogen recognition and self-tolerance, and explores the likelihood of autoimmune T cells escaping thymic deletion.

Contribution

It provides a computational and analytical model of thymic selection's role in shaping T cell receptor specificity and autoreactivity.

Findings

Thymic selection creates a T cell repertoire that balances pathogen recognition and self-tolerance.

The model predicts the probability of autoimmune T cells escaping thymic deletion.

Recognition of pathogenic peptides is both specific and degenerate in the modeled repertoire.

Abstract

T cells orchestrate adaptive immune responses upon activation. T cell activation requires sufficiently strong binding of T cell receptors on their surface to short peptides derived from foreign proteins bound to protein products of the major histocompatibility (MHC) gene products, which are displayed on the surface of antigen presenting cells. T cells can also interact with peptide-MHC complexes, where the peptide is derived from host (self) proteins. A diverse repertoire of relatively self-tolerant T cell receptors is selected in the thymus. We study a model, computationally and analytically, to describe how thymic selection shapes the repertoire of T cell receptors, such that T cell receptor recognition of pathogenic peptides is both specific and degenerate. We also discuss the escape probability of autoimmune T cells from the thymus.