Conventional and unconventional T cell receptor recognition

Human T cell analysis requires knowledge of the specificity (antigen target) and cellular functional profile. These analyses are complicated by the vast potential diversity of T cell receptors (estimated at >10⁶¹) and variation in presented target antigens determined by HLA. Here I will discuss approaches to deconstruct this complexity, utilizing TCR distance-based analysis and novel methods for integrating TCR sequence and single cell gene expression data. These approaches will be applied to studies of SARS-CoV-2 infection, influenza vaccination, and cancer to identify diverse T cell differentiation trajectories and clinically relevant associations with protected and susceptible phenotypes.