Modulation of antigen discrimination by duration of immune contacts in a kinetic proofreading model of T cell activation with extreme statistics.

ABSTRACT: T cells form transient cell-to-cell contacts with antigen presenting cells (APCs) to facilitate surface interrogation by membrane bound T cell receptors (TCRs). Upon recognition of molecular signatures (antigen) of pathogen, T cells may initiate an adaptive immune response. The duration of the T cell/APC contact is observed to vary widely, yet it is unclear what constructive role, if any, such variations might play in immune signaling. Modeling efforts describing antigen discrimination often focus on steady-state approximations and do not account for the transient nature of cellular contacts. Within the framework of a kinetic proofreading (KP) mechanism, we develop a stochastic First Receptor Activation Model (FRAM) describing the likelihood that a productive immune signal is produced befo

SUBMITTER: Morgan J 

PROVIDER: S-EPMC10497171 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature