Discrete protein condensation events govern calcium signal dynamics in T cells

Abstract

Calcium level variations, which occur downstream of T cell receptor (TCR) signaling, are an essential aspect of T cell antigen recognition. Although coordinated ion channel activities are known to drive calcium oscillations in other cell types, observations of nonperiodic and heterogeneous calcium patterns in T cells are inconsistent with this mechanism. Here, we track the complete ensemble of individual molecular peptide-major histocompatibility complex (pMHC) binding events to TCR, while simultaneously imaging LAT condensation events and calcium level. Individual LAT condensates induce a rapid and additive calcium response, which quickly attenuates upon condensate dissolution. No evidence of cooperativity between LAT condensates or oscillatory calcium response was detected. These results reveal stochastic LAT protein condensation events as a primary driver of calcium signal dynamics in T cells. One-Sentence SummaryCa2+ fluctuations in T cells reflect stochastic protein condensation events triggered by single molecular antigen-TCR binding.