CD8 MODULATION OF T-CELL ANTIGEN RECEPTOR-LIGAND INTERACTIONS ON LIVING CYTOTOXIC T-LYMPHOCYTES

THYMOCYTES and class I major histocompatibility complex (MHC)-restricted cytotoxic T lymphocytes express predominantly heterodimeric alpha/beta CD8(1,2). By interacting with non-polymorphic regions of MHC class I molecules CD8 can mediate adhesion(3-6) or by binding the same MHC molecules that interact with the T-cell antigen receptor (TCR) function as coreceptor in TCR-ligand binding and T-cell activation(1,2). Using TCR photoaffinity labelling with a soluble, monomeric photoreactive H-2K(d)-peptide derivative complex(7), we report here that the avidity of TCR-ligand interactions on cloned cytotoxic T cells is very greatly strengthened by CD8. This is primarily explained by coordinate binding of ligand molecules by CD8 and TCR, because substitution of Asp 227 of K-d with LYS severely impaired the TCR-ligand binding on CD8(+), but not CD8(-) cells. Kinetic studies on CD8(+) and CD8(-) cells further showed that CD8 imposes distinct dynamics and a remarkable temperature dependence on TCR-ligand interactions. We propose that the ability of CD8 to act as coreceptor can be modulated by CD8-TCR interactions.