Immunobiology of MAIT cells in the healthy and infected human host

T lymphocytes play many critical roles in immune protection of the human host.

Mucosa-associated invariant T (MAIT) cells are a large subset of unconventional, innate-like T cells that are highly abundant in mucosal tissues, liver and peripheral blood in humans.

MAIT cells recognize microbial vitamin B2 (riboflavin) metabolites from a wide range of microbes presented by the highly evolutionarily conserved and non-polymorphic MHC class I-like MR1 molecules.

MAIT cells thus represent an arm of cell-mediated immunity which recognize and respond to a principally novel and conserved type of antigenic structure.

Furthermore, recent findings indicate that MAIT cells also play important roles in viral infections, as well as in tissue repair. Nevertheless, many aspects of MAIT cell immunobiology and their role in infectious diseases remain unexplored.

The goals of the present proposal are to unravel the functional diversity and subset specialization of human MAIT cells, determine the roles they play in immune defense of human barrier tissues, and investigate the interplay between MAIT cell antimicrobial effector functions, bacterial immune evasion strategies and antimicrobial resistance.

We anticipate that the proposed investigations will significantly enhance our understanding of fundamental MAIT cell immunobiology, and of the roles MAIT cells play in immune defense against clinically important infections.