Extent of MHC Clustering Regulates Selectivity and Effectiveness of T Cell Responses.

ABSTRACT: MHC proteins that present peptide ligands for recognition by TCR form nanoscale clusters on the cell membrane of APCs. How the extent of MHC clustering controls productive TCR engagement and TCR-mediated signaling has not been systematically studied. To evaluate the role of MHC clustering, we exploited nanoscale discoidal membrane mimetics (nanolipoprotein particles) to capture and present peptide-MHC (pMHC) ligands at various densities. We examined the binding of these model membrane clusters to the surface of live human CD8⁺ T cells and the subsequent triggering of intracellular signaling. The data demonstrate that the proximity of pMHC ligands, high association rate of CD8-MHC interactions, and relatively long lifetime of cognate TCR-pMHC complexes emerge as essential paramet

SUBMITTER: Anikeeva N 

PROVIDER: S-EPMC6362847 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature