I have spent more than the last 40 years at the University of California, San Francisco
(UCSF), studying T cell receptor (TCR) signaling. I was blessed with supportive mentors, an …

T cell activation is a critical event in the adaptive immune response, indispensable for cell-
mediated and humoral immunity as well as for immune regulation. Recent years have …

Systems immunology lacks a framework with which to derive theoretical understanding from
high-dimensional datasets. We combined a robotic platform with machine learning to …

T cells use their T cell receptors (TCRs) to discriminate between lower-affinity self and
higher-affinity non-self peptides presented on major histocompatibility complex (pMHC) …

Mature T cells must discriminate between brief interactions with self-peptides and prolonged
binding to agonists. The kinetic proofreading model posits that certain T-cell antigen …

Kinetic proofreading (KPR) has been used as a paradigmatic explanation for the high
specificity of ligand discrimination by cellular receptors. KPR enhances the difference in the …

LAT assembly into a two-dimensional protein condensate is a prominent feature of antigen
discrimination by T cells. Here, we use single-molecule imaging techniques to resolve the …

Immune sentinel cells initiate immune responses to pathogens and tissue injury and are
capable of producing highly stimulus-specific responses. Insight into the mechanisms …

T cell responses are inhibited by acidic environments. T cell receptor (TCR)-induced protein
phosphorylation is negatively regulated by dephosphorylation and/or ubiquitination, but the …

T cells use kinetic proofreading to discriminate antigens by converting small changes in
antigen-binding lifetime into large differences in cell activation, but where in the signaling …