Fate of intercellular MHC-peptide-T-cell receptor complexes during T-cell activation.

Abstract

Antigen-specific T-cell activation requires the formation of a transient cell-cell conjugate between a T cell and an appropriate antigen presenting cell (APC). Focal aggregation of T-cell receptor (TCR) molecules at the T-cell-APC membrane interface accompanies formation of multiple non-covalent intercellular bridges consisting of TCRs on the T cell and cognate MHC-peptide complexes on the APC. Enhanced adhesiveness and T-cell activation follow the T-cell signalling that results from crosslinking of T-cell receptors (TCR). Models of T-cell activation propose that the APC and activated T cell separate following a decline in the enhanced adhesiveness. The rate of intercellular TCR-(MHC-peptide) complexes formed during T-cell activation is unknown. Based on the reported CD4-positive T-cell internalization of the peptide moiety of preformed cognate MHC II-peptide complexes, it is proposed here that translocation of the peptide moiety leads to destabilization and decomposition of intercellular trimolecular TCR-(MHC-peptide) complexes in the T-cell-APC interface. This decomposition accompanies or results in the decline in enhanced adhesiveness leading to separation of the APC and activated T cell.