THE SIGNAL SEQUENCE OF LYMPHOCYTIC CHORIOMENINGITIS VIRUS CONTAINS ANIMMUNODOMINANT CYTOTOXIC T-CELL EPITOPE THAT IS RESTRICTED BY BOTH H-2D(B) AND H-2K(B) MOLECULES

Infection of H-2(b) mice with lymphocytic choriomeningitis virus (LCMV ) generates three well-characterized H-2D(b)-restricted immunodominant epitopes delineated in the NP, GPI, and GP2 proteins. Here we report that the H-2D(b)-restricted GPI epitope GP33-41/43 (KAVYNFATC/GI) loca ted in the signal sequence of LCMV is also the immunodominant epitope recognized by CTL at the surface of the same infected cells in the con text of H-2K(b) restriction. The GP1 epitope bound to H-2D(b) and H-2K (b) molecules with comparable affinities. The respective binding proce sses involved different sets of peptide anchoring residues and require d dramatically different conformations of the peptide backbone as well as rearrangement of residue side chains. The 10-mer peptide GP34-43 ( AVYNFATCGI) was the optimal H-2K(b)-binding sequence and the 8-mer pep tide GP34-41 (AVYNFATC) the minimal sequence for optimal H-2K(b)-restr icted CTL recognition. Comparison of lytic activities of primary splen ic anti-LCMV CTL from C57BL/6 (Db+/Kb+), B10A.[5R] (Db-/Kb+), and B10A .[2R] (Db+/Kb-) mice against LCMV-infected or peptide-coated target ce lls expressing either one or the two MHC alleles revealed that the H-2 K(b)-restricted component of the anti-GP1 CTL response was mounted ind ependently of but as efficiently as its H-2D(b) counterpart. Analysis of the immune response against a GPI variant that escapes CTL recognit ion showed that the GP1 epitope: (i) was likely the only immunodominan t LCMV epitope in the context of H-2K(b), and (ii) could efficiently e vade H-2D(b) and H-2K(b)-restricted CTL mediated lysis. (C) 1997 Acade mic Press.