Requirements for Recognition of Epstein-Barr Virus-Infected Target Cells by Human Cytotoxic T Lymphocytes

Abstract

Epstein-Barr virus (EBV) is a widespread herpesvirus which infects the vast majority of individuals in all human populations worldwide. In most such individuals, infection occurs asymptomatic ally in childhood and leads to the establishment of a life-long virus carrier state. The virus is known to persist in at least two habitats in vivo: (1) in epithelial cells of the oropharynx from which infectious virus can be readily isolated, and (2) in peripheral blood B cells which when placed in culture give rise to continuously proliferating lymphoblastoid cell lines (LCLs). Such LCLs can also be easily produced by exposure of resting B cells to an exogenous source of EBV in vitro. The persistent infection in healthy EBV carriers is believed to be controlled by Cytotoxic Tlymphocytes (CTLS), since all such individuals possess CTL precursors in the circulating T cell pool which can be reactivated in vitro to lyse EBV-infected target B cells in an EBV-specific and HLA crass I antigen-restricted manner (Rickinson, 1986). It is now clear that efficient lysis of EBV+ target B cells by CTLs requires two phases of recognition, the first dependent upon cell adhesion molecules mediating an antigen-independent CTL-target cell conjugation, and the second involving specific recognition of viral target antigens by the T cell receptor (Gregory et al., 1988). These two aspects of the CTL recognition of EBV-infected target Bcells will be the subject of this brief review.