title: Identification of non-CSP antigens bearing CD8 epitopes in mice immunized with irradiated sporozoites.
abstract: Immunization of BALB/c mice with irradiated sporozoites (IrSp) of Plasmodium yoelii can lead to sterile immunity. The circumsporozoite protein (CSP) plays a dominant role in protection. Nevertheless after hyper-immunization with IrSp, complete protection is obtained in CSP-transgenic BALB/c mice that are T-cell tolerant to the CSP and cannot produce antibodies [CSP-Tg/JhT(-/-)]. This protection is mediated exclusively by CD8(+) T cells [1]. To identify the non-CSP protective T cell antigens, we studied the properties of 34 P. yoelii sporozoite antigens that are predicted to be secreted and to contain strong Kd-restricted CD8(+) T cell epitopes. The synthetic peptides corresponding to the epitopes were used to screen for the presence of peptide-specific CD8(+) T cells secreting interferon-γ (IFN-γ) in splenocytes from CSP-Tg/JhT(-/-) BALB/c mice hyper immunized with IrSp. However, the numbers of IFN-γ-secreting splenocytes specific for the non-CSP antigen-derived peptides were 20-100 times lower than those specific for the CSP-specific peptide. When mice were immunized with recombinant adenoviruses expressing selected non-CSP antigens, the animals were not protected against challenge with P. yoelii sporozoites although large numbers of CD8(+) specific T cells were generated.
authors.affiliation: Michael Heidelberger Division, Department of Pathology, New York University School of Medicine, NY 10016, United States. satish.mishra@nyumc.org
authors.forename: Satish
authors.initials: S
authors.lastname: Mishra
authors.forename: Urvashi
authors.initials: U
authors.lastname: Rai
authors.forename: Takayuki
authors.initials: T
authors.lastname: Shiratsuchi
authors.forename: Xiangming
authors.initials: X
authors.lastname: Li
authors.forename: Yannick
authors.initials: Y
authors.lastname: Vanloubbeeck
authors.forename: Joe
authors.initials: J
authors.lastname: Cohen
authors.forename: Ruth S
authors.initials: RS
authors.lastname: Nussenzweig
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Winzeler
authors.forename: Moriya
authors.initials: M
authors.lastname: Tsuji
authors.forename: Victor
authors.initials: V
authors.lastname: Nussenzweig
mesh_terms: D000256:Adenoviridae / Q000235:genetics / Q000276:immunology; D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D007114:Immunization; D007371:Interferon-gamma; D008288:Malaria / Q000276:immunology / Q000517:prevention & control; D017780:Malaria Vaccines / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D010967:Plasmodium yoelii / Q000276:immunology*; D015800:Protozoan Proteins / Q000276:immunology*; D034101:Sporozoites / Q000276:immunology* / Q000528:radiation effects
chemical_list: D000953:Antigens, Protozoan; D018984:Epitopes, T-Lymphocyte; D017780:Malaria Vaccines; D015800:Protozoan Proteins; C041595:circumsporozoite protein, Protozoan; D007371:Interferon-gamma