Role of MAIT cells in COVID-19 immunopathogenesis and in the mRNA vaccine response

Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) causes the coronavirus disease COVID-19. Severe COVID-19 cases are characterized by lymphopenia and aberrant inflammatory immune activation in the lung.

Mucosa-associated invariant T (MAIT) cells are a large subset of unconventional T cells with innate-like response characteristics that are highly abundant in lung and peripheral blood.

MAIT cells exhibit strong tissue tropism and inflammatory potential, when activated by microbial metabolites presented by MHC-like molecule MR1 or by inflammatory signals.

MAIT cells also play important roles in viral diseases as sensors of infection, and our recent data show that MAIT cells are strongly engaged in severe COVID-19 disease.

The goals of the present proposal are (1) to determine the ability of MAIT cells and their antimicrobial function to recover in COVID-19 convalescent patients, (2) to dissect the response of MAIT cells to SARS-CoV-2 in vitro, and (3) to investigate the role of MAIT cell viral sensor responses in the initiation of adaptive immune responses to COVID-19 mRNA vaccination.

This research proposal builds on our expertise and strong position in the MAIT cell field built over the last decade.

We anticipate that the proposed investigations will significantly enhance our understanding of the role unconventional T cells play in COVID-19 immunopathogenesis and mRNA vaccine responses.