TCR-Mediated Internalization of Peptide-MHC Complexes Acquired by T Cells

Peptide-major histocompatibility complex protein complexes (pMHCs) on antigen-presenting cells (APCs) are central to T cell activation. Within minutes of peptide-specific T cells interacting with APCs, pMHCs on APCs formed clusters at the site of T cell contact. Thereafter, these clusters were acquired by T cells and internalized through T cell receptor-mediated endocytosis. During this process, T cells became sensitive to peptide-specific lysis by neighboring T cells (fratricide). This form of immunoregulation could explain the "exhaustion" of T cell responses that is induced by high viral loads and may serve to down-regulate immune responses.