Molecular interactions in the activation of effector and precursor cytotoxic T lymphocytes

Abstract

Cell-cell interactions are influenced by parameters that cannot readily be studied using either intact cells or soluble molecules. Replacing one of the pair of interacting cells with an artificial cell surface construct allows novel insights to be gained into some of these parameters. Application of this approach to the study of CTL has helped to clarify the contrasting roles of some of the various receptors that are involved in recognition, adhesion and activation. In addition, it has revealed features of these receptor ligand interactions that help to explain how CTL are able to carry out effective immune surveillance and elimination of virus-infected or tumor cells. Although not discussed in this review, artificial cell surface constructs have also been effectively employed to study the interaction of TH cells with class II bearing surfaces. Class I protein and peptide antigen can be sufficient to mediate adhesion and activate CTL effector function through the TCR and CD8. In addition, interactions of other co-receptors with their ligands can act along with TCR and CD8 in a cascade of activated adhesion and co-stimulatory signal generation to allow adhesion and response when antigen and/or class I surface densities are too low to be sufficient by themselves to initiate response. The relative contributions of the various receptor/ligand interactions to a given CTL/target encounter will depend upon the affinity of the TCR for antigen and on the densities and types of ligands, including antigen, displayed on the target cell surface. It appears that the CTL has the ability to accomplish its task in a variety of ways, providing it with considerable flexibility in recognizing and eliminating antigen-bearing target cells. Thus, downregulation of any one particular ligand on a virus-infected or tumor cell does not allow escape from CTL surveillance provided that at least a low level of class I antigen remains present. The CTL is able to employ several co-receptors specific for ligands common to many cell types without being diverted from effective immune surveillance, since these receptors only become activated to mediate high-avidity adhesion when antigen is detected by the TCR. Cloned effector CTL are most amenable to studies of the kind reviewed here, since large numbers of homogenous cells can be obtained, antigen-specific adhesion can be readily measured and response is rapid and easily quantitated.(ABSTRACT TRUNCATED AT 400 WORDS)