CROSS-PROTECTION AGAINST LYMPHOCYTIC CHORIOMENINGITIS VIRUS MEDIATED BY A CD4-CELL CLONE SPECIFIC FOR AN ENVELOPE GLYCOPROTEIN EPITOPE OF LASSA VIRUS( T)

Recombinant vaccinia virus expressing the Lassa virus (LV) envelope gl ycoprotein precursor, V-LSGPC, was used to study the basis of LV-induc ed cross-protective immunity against the closely related arenavirus ly mphocytic choriomeningitis virus (LCMV). C3H/Hej mice primed with V-LS GPC developed neither circulating antibodies nor CD8+ cytotoxic T cell s specific for LCMV, yet they resisted a normally lethal LCMV challeng e. Spleen cells from such mice gave a proliferative response to LCMV i n vitro that was inhibitable by anti-CD4 antibody. Synthetic peptides corresponding to predicted T-cell sites common to the envelope glycopr otein precursor (GP-C) of LV and that of LCMV were used to map the spe cificity of the proliferative response to an epitope located between a mino acids 403 and 417 of LV GP-C. Several CD4+ T-cell clones specific for the 403-417 peptide were isolated and found to produce gamma inte rferon in response to both the peptide and LCMV. One of these clones, C9, was selected for further study. C9 lysed I-A(K)-bearing target cel ls, and when adoptively transferred to C3H/Hej mice, it was capable of mediating both a peptide-specific delayed hypersensitivity reaction a nd resistance to lethal LCMV challenge. These collective findings demo nstrate, for the first time, that CD4+ T cells can play a major role i n arenavirus-specific cross-protective immunity.