Dr. Huang’s studies have been focused on the activation and
function of T cells in infectious and inflammatory diseases. During his
postdoctoral training with Ted Hansen at Washington University, he started
understanding the activation mechanism of innate-like T cells, specifically the
mucosal-associated invariant T cells (MAIT) that are restricted by MHC class I
like molecule MR1. He generated three major findings including the requirement
of an antigen for MAIT cell activation (J
Biol Chem, 2005), endocytic pathway of MAIT cell antigen loading (J Exp Med, 2008), and innate-like
recognition of MR1 antigen complex by semi-invariant MAIT T cell receptor (PNAS, 2009). These findings supported the
hypothesis that MAIT cells bear a rapid innate-like activation mechanism able to
uniquely regulate mucosal diseases (Nat
Immunol, 2007 review) and further inspired the discovery of MAIT cell
protection against mycobacterial infection (Nat
Immunol, 2010). As the lipid-responding T cells also show similar
innate-like activation features, Dr. Huang’s additional training with Branch Moody
at Harvard Medical School helped him establish a metabolomic platform and its
applications to the antigens presented by MHC class I like CD1 proteins for the
activation of lipid-responding T cells. These studies firstly revealed that the
CD1b scaffold lipid diacylglycerol facilitates the presentation of the antigen
mycobacterial glucose monomycolate to activate T cells from human tuberculosis
(PNAS, 2011). Further collaboration
using his metabolomic platform has discovered that mycobacterial and host lipid
antigens were able to activate CD1c and CD1a-restricted T cells (J Exp Med, 2013, Nature Immunol, 2013).
Dr. Huang is extending the studies on the activation
mechanisms and antigen structures of innate-like T cells particularly to the
settings of mycobacterial infection, gut inflammation, and environmental exposure.