Parallel reactions on a single T cell receptor offer a robust kinetic proofreading mechanism.

ABSTRACT: T cells can recognize a few molecules of cognate antigen among vastly outnumbering noncognate ligands. The T cell receptor (TCR) differentiates antigens based on antigen-TCR binding dwell time through a kinetic proofreading process. Historically, this has been modeled as the ligated receptor undergoing a series of reactions before producing a signal. In such a sequential mechanism, the number of steps is a key determinant of discrimination fidelity. Here, we consider two features of the molecular mechanism of TCR activation that diverge from a sequential process and suggest that an alternative kinetic proofreading mechanism may be at play. First, activation processes of multiple ITAM domains of the TCR represent parallel reaction sequences taking place on a single TCR molecule. Second, the

SUBMITTER: Morita S 

PROVIDER: S-EPMC12519229 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature