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T Cell Responses to Arenavirus Infections.

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Final rept. 17 Aug 89-31 Aug 91,

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The immunological basis of the reciprocal cross-immunity induced by lymphocytic choriomeningitis virus LCMV and Lassa virus LV was investigated. A recombinant vaccinia virus that expresses the LV envelope glycoprotein precursor molecule, GP-C, Vac-LV-G protects C3HHeJ mice against lethal challenge with LCMV UBC. Protection correlated with the induction of T helper cells, but not cytotoxic T cells, that recognize LCMV antigens in vitro. Using synthetic peptides corresponding to potential T cell sites on LV GP-C we found that Vac-LV-G and LCMV induce a population of CD4 T cells that recognize an epitope located between residues 403-417 of LV GP-C GP-C403-417. A synthetic peptide corresponding to these residues stimulated proliferation and IFN Gamma secretion by T cells primed with either virus. Five CD4 T cell clones specific for GP-C403-417 were derived from Vac-LV-G-primed mice. Of the four clones that secreted IFN GAMMA in response to the peptide, three of them also recognized LCMV in vitro. Two clones clones 9 and 1 1 are 1-Ak-restricted and lyse target cells bearing the appropriate restriction elements in the presence of the peptide. T cell clone 9 mediates a peptide-specific delayed type hypersensitivity reaction and adoptively protects C3HHeJ mice against lethal challenge with LCMV. T cells Arenaviruses Hemorrhagic fevers, Lassa fever, LCMV Lassa fever virus Synthetic peptides Vaccine Recombinant vaccinia GP-C CD4 T cell clones RA 1.

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  • Medicine and Medical Research

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