CD8 modulation of T-cell antigen receptor–ligand interactions on living cytotoxic T lymphocytes

Abstract

THYMOCYTES and class I major histocompatibility complex (MHC)-restricted cytotoxic T lymphocytes express predominantly heterodimeric α/β 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 complex⁷, 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.