Cross-protection against lymphocytic choriomeningitis virus mediated by a CD4+ T-cell clone specific for an envelope glycoprotein epitope of Lassa virus.
Recombinant vaccinia virus expressing the Lassa virus (LV) envelope glycoprotein precursor, V-LSGPC, was used to study the basis of LV-induced cross-protective immunity against the closely related arenavirus lymphocytic choriomeningitis virus (LCMV). C3H/HeJ mice primed with V-LSGPC developed neither circulating antibodies nor CD8+ cytotoxic T cells specific for LCMV, yet they resisted a normally lethal LCMV challenge. Spleen cells from such mice gave a proliferative response to LCMV in vitro that was inhibitable by anti-CD4 antibody. Synthetic peptides corresponding to predicted T-cell sites common to the envelope glycoprotein precursor (GP-C) of LV and that of LCMV were used to map the specificity of the proliferative response to an epitope located between amino 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 interferon in response to both the peptide and LCMV. One of these clones, C9, was selected for further study. C9 lysed I-AK-bearing target cells, and when adoptively transferred to C3H/HeJ mice, it was capable of mediating both a peptide-specific delayed hypersensitivity reaction and resistance to lethal LCMV challenge. These collective findings demonstrate, for the first time, that CD4+ T cells can play a major role in arenavirus-specific cross-protective immunity.
La Posta
V J
VJ
Department of Microbiology and Immunology, University of Maryland, Baltimore 21201.
Auperin
D D
DD
Kamin-Lewis
R
R
Cole
G A
GA
D000595:Amino Acid Sequence; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D016827:CD8 Antigens / Q000276:immunology; D002999:Clone Cells / Q000276:immunology; D003429:Cross Reactions; D003602:Cytotoxicity, Immunologic; D000939:Epitopes / Q000276:immunology; D015686:Gene Products, env / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007114:Immunization; D007371:Interferon-gamma / Q000096:biosynthesis; D007836:Lassa virus / Q000276:immunology*; D008216:Lymphocytic Choriomeningitis / Q000276:immunology / Q000517:prevention & control*; D051379:Mice; D008809:Mice, Inbred C3H; D008969:Molecular Sequence Data; D011994:Recombinant Proteins / Q000276:immunology; D013154:Spleen / Q000276:immunology; D014616:Vaccinia virus / Q000235:genetics
D016827:CD8 Antigens; D000939:Epitopes; D015686:Gene Products, env; D011994:Recombinant Proteins; D007371:Interferon-gamma