Optimal Lymphocytic Choriomeningitis Virus Sequences Restricted by H-2Db Major Histocompatibility Complex Class I Molecules and Presented to Cytotoxic T Lymphocytes

Overview

Journal J Virol

Publisher American Society for Microbiology

Date 1995 Apr 1

PMID 7533855

Citations 47

Authors

J E Gairin

H Mazarguil

D Hudrisier

M B Oldstone

Affiliations

Soon will be listed here.

Abstract

Infection with lymphocytic choriomeningitis virus induces the generation of CD8+ cytotoxic T lymphocytes (CTL). In the H-2b mouse, this cellular immune response is directed against three viral structural epitopes (GP1, GP2, and NP) presented by the major histocompatibility complex (MHC) class I H-2Db molecules. This study was undertaken to delineate which sequence of each of these three epitopes is optimal for MHC binding and CTL recognition. The first step was to synthesize the relevant peptides truncated at the N or C terminus and flanking the crucial H-2Db-anchoring Asn residue in position 5. These peptides were then tested (i) for their binding properties in two H-2Db-specific assays with viable cells (upregulation of H-2Db expression on the surface of RMA-S cells and competition against the Db-restricted peptide 125I-gp276-286 on T2-Db cells) and (ii) for their abilities to sensitize H-2b target cells for CTL lysis in vitro. For optimal antigenic presentation, all three epitopes required the MHC-anchoring Asn residue at position 5 of their sequences. The results clearly and unambiguously delineated optimal lengths for two of the epitopes and two options for the third. NP appeared as a conventional 9-amino-acid (aa)-long peptide, np396-404 (FQPQNGQFI). GP2 was defined as a longer peptide (11 aa), gp276-286 (SGVENPGGYCL). Characterization of the GP1 epitope was more complex: the 9-aa-long peptide gp33-41 (KAVYNFATC) and the carboxyl-extended 11-aa-long peptide gp33-43 (KAVYN FATCGI) were both established as possible optimal sequences depending on the cell line used to test binding and lysis.

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