title: Characterization of T-helper epitopes of the glycoprotein of vesicular stomatitis virus.
abstract: The T-helper (Th) cell epitopes in the glycoprotein (GP) of vesicular stomatitis virus serotype Indiana (VSV-IND) were analyzed with a complete panel of overlapping synthetic peptides. Three Th-cell epitopes in C57BL/6 (H-2b) mice and two epitopes in BALB/c (H-2d) mice were defined by their ability to stimulate in vitro proliferation of virus-primed, CD8+ T-cell-depleted spleen cells in a class II-restricted manner. A series of CD4+, I-Ab-restricted T-cell hybridomas from VSV-primed C57BL/6 mice were characterized by their production of interleukin-2 and interleukin-3 upon stimulation with VSV-IND or purified VSV GP in vitro. Of nine hybridomas derived from three independent fusions, five were specific for amino acids (aa) 415 to 433 (p8) of VSV-IND GP, three recognized aa 52 to 71 (p41), and one reacted against aa 316 to 335 (p17). Fluorocytometric analysis of Th hybridomas or VSV-stimulated T-cell lines with monoclonal antibodies specific for the T-cell receptor V beta chain did not reveal obvious correlations between the T-cell receptor V beta gene segment used and the epitope recognized. All three peptides recognized by H-2b mice and both epitopes recognized by H-2d mice which were characterized in primed T-cell populations were capable of activating specific Th cells in vivo as measured by the induction of antibody class switch from immunoglobulin M (IgM) to IgG. Thus, the epitopes are relevant for VSV GP-specific Th response in vivo and are able to provide functional help for the production of anti-VSV-specific neutralizing IgG antibodies.
authors.affiliation: Department of Pathology, Institute for Experimental Immunology, Zürich, Switzerland.
authors.forename: C
authors.initials: C
authors.lastname: Burkhart
authors.forename: G
authors.initials: G
authors.lastname: Freer
authors.forename: R
authors.initials: R
authors.lastname: Castro
authors.forename: L
authors.initials: L
authors.lastname: Adorini
authors.forename: K H
authors.initials: KH
authors.lastname: Wiesmüller
authors.forename: R M
authors.initials: RM
authors.lastname: Zinkernagel
authors.forename: H
authors.initials: H
authors.lastname: Hengartner
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000939:Epitopes / Q000276:immunology*; D006183:H-2 Antigens / Q000235:genetics; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007134:Immunoglobulin Switch Region / Q000276:immunology; D007156:Immunologic Memory; D007376:Interleukin-2 / Q000096:biosynthesis; D007377:Interleukin-3 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D014721:Vesicular stomatitis Indiana virus / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000276:immunology*
chemical_list: D000939:Epitopes; C028391:G protein, vesicular stomatitis virus; D006183:H-2 Antigens; D000949:Histocompatibility Antigens Class II; D007376:Interleukin-2; D007377:Interleukin-3; D008562:Membrane Glycoproteins; D010446:Peptide Fragments; D016693:Receptors, Antigen, T-Cell, alpha-beta; D014759:Viral Envelope Proteins