A new homeostatic model of the T cell system

TL;DR

This paper proposes a novel homeostatic model of the T cell system emphasizing the role of positive thymic selection in maintaining immune equilibrium and indirect recognition of infections through a self-mirror mechanism.

Contribution

It introduces a new logic-based model distinguishing homeostatic and infection-specific T cell populations, differing from conventional models.

Findings

Homeostatic T cells recognize infections indirectly via self-MHC-peptide complexes.

The model explains how T cell populations maintain immune balance.

Infection-specific T cells arise separately and do not enter the thymus.

Abstract

Our main tenet argues that the primary role of positive thymic selection and the resulting T cell population is the maintenance of a homeostatic equilibrium with self MHC-self peptide complexes. The homeostatic T cell repertoire can recognize infections non-specifically and this is an indirect (negative) recognition: the whole homeostatic T cell population together "holds a mirror" to the whole self, and any MHC-peptide complex that is "not reflected in the mirror" can be perceived by surrounding homeostatic T cells as a signal of the presence of a foreign entity. On the other hand, infection-specific T cell clones arise in a different pathway in the periphery, do not enter the thymus, and form a functionally different population. Here we summarize the basic assumptions and consequences of a logic-based new model, which differs from conventional models in many respects.