Project Grant K99AI201798

The National Institute of Allergy and Infectious Diseases awarded The Leland Stanford Junior University $166,425 on August 3, 2026, under the Allergy and Infectious Diseases Research program (CFDA 93.855, Project Grant K99AI201798).

The recipient will systematically map the antigen specificity of approximately 1,000 T cell receptors (TCRs) from intestinal CD4+ T cell populations to characterize how microbiota and dietary components determine CD4 T cell fate. The research employs a gnotobiotic mouse model naturally colonized from birth with a 116-strain human microbiota paired with a high-throughput platform to clone and characterize native TCR specificity at single-cell resolution. The work tests whether regulatory T cell (Treg) induction represents the default outcome of foreign antigen recognition in the healthy gut, challenging the prevailing paradigm that distinct microbial taxa preferentially induce particular CD4+ T cell lineages. Preliminary results show that microbiota- and diet-reactive TCRs are overwhelmingly enriched in the induced Treg lineage, while effector cells exhibit little reactivity. Findings will inform understanding of dysregulated CD4+ T cell responses implicated in inflammatory bowel diseases, food allergy, and infectious diseases.

Performance occurs in Palo Alto, California. The award period runs through July 31, 2028.