If. Luescher et al., CD8 MODULATION OF T-CELL ANTIGEN RECEPTOR-LIGAND INTERACTIONS ON LIVING CYTOTOXIC T-LYMPHOCYTES, Nature, 373(6512), 1995, pp. 353-356
THYMOCYTES and class I major histocompatibility complex (MHC)-restrict
ed cytotoxic T lymphocytes express predominantly heterodimeric alpha/b
eta 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) functio
n as coreceptor in TCR-ligand binding and T-cell activation(1,2). Usin
g 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 greatl
y strengthened by CD8. This is primarily explained by coordinate bindi
ng 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(+), b
ut not CD8(-) cells. Kinetic studies on CD8(+) and CD8(-) cells furthe
r showed that CD8 imposes distinct dynamics and a remarkable temperatu
re dependence on TCR-ligand interactions. We propose that the ability
of CD8 to act as coreceptor can be modulated by CD8-TCR interactions.