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.