Evolutionary Perspective of Nonclassical MHC Class I and Innate-like T Cells Relevance in Immune Surveillance

TL;DR

This review explores the role of nonclassical MHC class I molecules and innate-like T cells in immune surveillance from an evolutionary perspective.

Contribution

The paper provides a comprehensive evolutionary analysis of MHC-Ib molecules and innate-like T cells in immune function.

Findings

Innate-like T cells have limited TCR diversity and rely on nonpolymorphic MHC-Ib molecules.

Evolutionarily conserved subsets of innate-like T cells exist in mammals and amphibians.

Nonpolymorphic MHC-Ib genes are widespread in jawed vertebrates, suggesting broader immune roles.

Abstract

Unlike conventional T cells, which express a highly diverse repertoire of dimeric αβ T-cell receptors (TCRs) restricted by classical, polymorphic MHC class I molecules (MHC-Ia), a distinct group of T cells—collectively termed “innate-like T (iT) cells”—exhibits limited TCR diversity and depends instead on nonclassical, nonpolymorphic MHC class I molecules (MHC-Ib) for their development and function. While mounting evidence supports the role of iT cells as pivotal regulators and effectors in both innate and adaptive immune responses, many aspects of their biology remain incompletely understood. In humans, iT cells represent a significant fraction of the total T cell population, and evolutionarily conserved subsets have also been identified in other mammals and amphibians. Moreover, the expanding catalog of nonpolymorphic MHC-Ib genes and lineages—distinct from polymorphic MHC-Ia genes—across jawed vertebrate genomes suggests a broader and potentially more integral role for MHC-Ib molecules in T cell function and immune surveillance. In this review, we explore the immunological significance of MHC-Ib molecules and iT cells through an evolutionary lens, highlighting recent advances that shed light on their contributions to immune homeostasis and defense.

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