title: Circumsporozoite protein-specific K(d)-restricted CD8+ T cells mediate protective antimalaria immunity in sporozoite-immunized MHC-I-K(d) transgenic mice.
abstract: Although the roles of CD8+ T cells and a major preerythrocytic antigen, the circumsporozoite (CS) protein, in contributing protective antimalaria immunity induced by radiation-attenuated sporozoites, have been shown by a number of studies, the extent to which these players contribute to antimalaria immunity is still unknown. To address this question, we have generated C57BL/6 (B6) transgenic (Tg) mice, expressing K(d) molecules under the MHC-I promoter, called MHC-I-K(d)-Tg mice. In this study, we first determined that a single immunizing dose of IrPySpz induced a significant level of antimalaria protective immunity in MHC-I-K(d)-Tg mice but not in B6 mice. Then, by depleting various T-cell subsets in vivo, we determined that CD8+ T cells are the main mediator of the protective immunity induced by IrPySpz. Furthermore, when we immunized (MHC-I-K(d)-Tg × CS-Tg) F1 mice with IrPySpz after crossing MHC-I-K(d)-Tg mice with PyCS-transgenic mice (CS-Tg), which are unable to mount PyCS-specific immunity, we found that IrPySpz immunization failed to induce protective antimalaria immunity in (MHC-I-K(d)-Tg × CS-Tg) F1 mice, thus indicating the absence of PyCS antigen-dependent immunity in these mice. These results indicate that protective antimalaria immunity induced by IrPySpz in MHC-I-K(d)-Tg mice is mediated by CS protein-specific, K(d)-restricted CD8+ T cells.
authors.affiliation: HIV and Malaria Vaccine Program, Aaron Diamond AIDS Research Center, Affiliate of The Rockefeller University, 455 First Avenue, New York, NY 10016, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Huang
authors.affiliation: HIV and Malaria Vaccine Program, Aaron Diamond AIDS Research Center, Affiliate of The Rockefeller University, 455 First Avenue, New York, NY 10016, USA.
authors.forename: Tiffany
authors.initials: T
authors.lastname: Tsao
authors.affiliation: Department of Pathology, New York University School of Medicine, 545 First Avenue, New York, NY 10016, USA.
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.affiliation: HIV and Malaria Vaccine Program, Aaron Diamond AIDS Research Center, Affiliate of The Rockefeller University, 455 First Avenue, New York, NY 10016, USA.
authors.forename: Moriya
authors.identifier: 0000-0001-8587-277X
authors.initials: M
authors.lastname: Tsuji
mesh_terms: D000818:Animals; D000852:Anopheles; D000962:Antimalarials / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000378:metabolism*; D007114:Immunization; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010967:Plasmodium yoelii / Q000276:immunology / Q000378:metabolism; D034101:Sporozoites / Q000276:immunology* / Q000378:metabolism*
chemical_list: D000962:Antimalarials; D015395:Histocompatibility Antigens Class I