title: Localization of T helper cell epitopes in the vesicular stomatitis virus: the nucleoprotein is responsible for serotype cross-reactive T help.
abstract: The glycoprotein (G) of vesicular stomatitis virus (VSV) is known to contain the biologically relevant sites for virus-neutralizing antibodies as well as T helper (Th) cell epitopes. The capacity of other VSV proteins to elicit potent Th cell responses has not yet been investigated. Additionally, a short-lived cross-reactivity between the two serologically distinct VSV serotypes Indiana (IND) and New Jersey (NJ) on the T helper cell level has been reported. Here we address the question of whether the VSV nucleoprotein (N) or matrix protein (M) can elicit T help to VSV-G-specific B cells and which of the VSV proteins contains the elements responsible for the IND/NJ cross-reactivity. The N, G, and M of the VSV Indiana serotype produced in a recombinant baculovirus system were assayed for the ability to activate VSV-specific Th cells to induce immunoglobulin class switch of neutralizing antibody responses in vivo in C57BL/6 (H-2b) mice. All three VSV-IND proteins helped in the production of neutralizing IgG antibodies to the homologous VSV-Indiana serotype but only VSV-IND N was able to trigger an IgG response to the heterologous VSV-New Jersey serotype. This data suggest that Th epitope(s) in the VSV-IND N are responsible for the observed cross-reactivity of T helper cells.
authors.affiliation: Department of Pathology, Institute of Experimental Immunology, Zürich, Switzerland.
authors.forename: C
authors.initials: C
authors.lastname: Burkhart
authors.forename: G
authors.initials: G
authors.lastname: Freer
authors.forename: U
authors.initials: U
authors.lastname: Steinhoff
authors.forename: Y
authors.initials: Y
authors.lastname: Li
authors.forename: D H
authors.initials: DH
authors.lastname: Bishop
authors.forename: R M
authors.initials: RM
authors.lastname: Zinkernagel
authors.forename: H
authors.initials: H
authors.lastname: Hengartner
mesh_terms: D000818:Animals; D000956:Antigens, Viral / Q000276:immunology*; D002213:Capsid / Q000276:immunology*; D002460:Cell Line; D003429:Cross Reactions; D000939:Epitopes / Q000276:immunology*; D007114:Immunization; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000276:immunology; D007075:Immunoglobulin M / Q000096:biosynthesis / Q000276:immunology; D008562:Membrane Glycoproteins; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009500:Neutralization Tests; D017924:Nucleopolyhedroviruses / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000276:immunology; D012703:Serotyping; D018411:Spodoptera; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D014721:Vesicular stomatitis Indiana virus / Q000145:classification / Q000276:immunology*; D018116:Vesiculovirus; D014758:Viral Core Proteins / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000276:immunology; D014763:Viral Matrix Proteins / Q000276:immunology
chemical_list: D000956:Antigens, Viral; D000939:Epitopes; C028391:G protein, vesicular stomatitis virus; D007074:Immunoglobulin G; D007075:Immunoglobulin M; C094460:M protein, Vesicular stomatitis virus; D008562:Membrane Glycoproteins; D011993:Recombinant Fusion Proteins; D014758:Viral Core Proteins; D014759:Viral Envelope Proteins; D014763:Viral Matrix Proteins