FINE DISSECTION OF A NINE AMINO ACID GLYCOPROTEIN EPITOPE, A MAJOR DETERMINANT RECOGNIZED BY LYMPHOCYTEC CHORIOMENINGITIS VIRUS-SPECIFIC CLASS I-RESTRICTED H-2Db CYTOTOXIC T LYMPHOCYTES

Before lysing an infected cell, CTL must first recognize a discrete viral protein sequence in the context of a restricting protein of the MHC on the cell (1). CTL play a significant role in terminating viral infection (2-9), and the inability to generate them can alter the outcome of viral invasion from an acute, self-limiting infection to a persistent, continuous one (10) . Adoptive reconstitution of persistently infected hosts with previously primed virus-specific H-2-restricted CTLterminates the otherwise life-long infection (11) . Yet, despite the role of CTL in influencing the outcome of infection, except primarily for studies with influenza virus (12-16), relatively little is known about the precise protein sequence(s) that CTL recognize, especially glycoproteins, and their relationship to restriction elements within the MHC. To define the molecules involved in CTL recognition, we chose the model of lymphocytic choriomeningitis virus (LCMV)' in mice for several reasons. LCMV is a natural pathogen of mice (17), and the genetics of the mouse MHC is well understood and easily manipulated (18) . CTL specific for LCMV are readily obtained and constitute a majorimmune response in vivo for terminating acute infection (2, 5, 17). Their absence is associated with persistent infection (1, 2, 11) . Hence, data obtained from in vitro experimentation can be tested in vivo within a natural hostvirus model. LCMV has two RNA segments, a large (L) one of -7 .5 kb and a short (S) segment of 3 .3 kb ; CTL induction and recognition map to proteins encoded by genes on the S RNA (19, 20). The S RNA of LCMV Armstrong (ARM) encodes a 498 amino acid (aa) glycoprotein (GP) from its 5' ORFthat is posttranslationally cleaved at residues 262-263 to yield GP-1 (aa 1-262) and GP-2 (aa 263-498) and a 558-aa nucleoprotein (NP) made from the 3' ORF (21,22). Earlier studies using cDNAs of LCMV GP or LCMV NP expressed in vaccinia virus (23, 24) indicated that the