title: Vaccinia virus-specific CD4+ T cell responses target a set of antigens largely distinct from those targeted by CD8+ T cell responses.
abstract: Recent studies have defined vaccinia virus (VACV)-specific CD8(+) T cell epitopes in mice and humans. However, little is known about the epitope specificities of CD4(+) T cell responses. In this study, we identified 14 I-A(b)-restricted VACV-specific CD4(+) T cell epitopes by screening a large set of 2146 different 15-mer peptides in C57BL/6 mice. These epitopes account for approximately 20% of the total anti-VACV CD4(+) T cell response and are derived from 13 different viral proteins. Surprisingly, none of the CD4(+) T cell epitopes identified was derived from VACV virulence factors. Although early Ags were recognized, late Ags predominated as CD4(+) T cell targets. These results are in contrast to what was previously found in CD8(+) T cells responses, where early Ags, including virulence factors, were prominently recognized. Taken together, these results highlight fundamental differences in immunodominance of CD4(+) and CD8(+) T cell responses to a complex pathogen.
authors.affiliation: Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA.
authors.forename: Magdalini
authors.initials: M
authors.lastname: Moutaftsi
authors.forename: Huynh-Hoa
authors.initials: HH
authors.lastname: Bui
authors.forename: Bjoern
authors.initials: B
authors.lastname: Peters
authors.forename: John
authors.initials: J
authors.lastname: Sidney
authors.forename: Shahram
authors.initials: S
authors.lastname: Salek-Ardakani
authors.forename: Carla
authors.initials: C
authors.lastname: Oseroff
authors.forename: Valerie
authors.initials: V
authors.lastname: Pasquetto
authors.forename: Shane
authors.initials: S
authors.lastname: Crotty
authors.forename: Michael
authors.initials: M
authors.lastname: Croft
authors.forename: Elliot J
authors.initials: EJ
authors.lastname: Lefkowitz
authors.forename: Howard
authors.initials: H
authors.lastname: Grey
authors.forename: Alessandro
authors.initials: A
authors.lastname: Sette
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000956:Antigens, Viral / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D018984:Epitopes, T-Lymphocyte / Q000378:metabolism; D006183:H-2 Antigens / Q000378:metabolism*; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D016056:Immunodominant Epitopes / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D011485:Protein Binding / Q000276:immunology; D014615:Vaccinia / Q000276:immunology / Q000821:virology; D014616:Vaccinia virus / Q000276:immunology*
chemical_list: D000956:Antigens, Viral; D018984:Epitopes, T-Lymphocyte; D006183:H-2 Antigens; D000949:Histocompatibility Antigens Class II; D016056:Immunodominant Epitopes