title: Generation of tissue-specific H-2Kd transgenic mice for the study of K(d)-restricted malaria epitope-specific CD8+ T-cell responses in vivo.
abstract: CD8(+) T cells are critical for the control of various intracellular infections and cancers. To date, however, effective T cell-based vaccines remain elusive, due, in part, to the lack of in vivo models that facilitate the dissection of antigen-specific CD8(+) T-cell responses primed by different antigen-presenting cells (APCs). In this study, we generated four lines of H-2K(d) transgenic (K(d) Tg) mice that differed in their expression of H-2K(d): dendritic cells (DCs) only (CD11c-K(d)), macrophages only (huCD68-K(d)), hepatocytes only (Alb-K(d)), or all nucleated cells (major histocompatibility complex-I-K(d)). Immunization of each of these K(d) Tg mouse strains with a synthetic peptide or a recombinant adenovirus expressing a well-known immunodominant, H-2K(d)-restricted CD8(+) T-cell epitope, SYVPSAEQI, which was derived from the circumsporozoite protein of Plasmodium yoelii, promoted distinct SYVPSAEQI-specific CD8(+) T-cell responses. The route of immunization also greatly influenced the magnitude of the epitope-specific CD8(+) T-cell response. These tissue-specific K(d) Tg mice may be valuable tools for determining the mode of induction of CD8(+) T-cell responses by different APCs in vivo and for characterizing the CD8(+) T-cell responses promoted in response to various microbial infections and/or different types of vaccines.
authors.affiliation: HIV and Malaria Vaccine Program, Aaron Diamond AIDS Research Center, Affiliate of the Rockefeller University, New York, NY 10016, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Huang
authors.forename: Xiangming
authors.initials: X
authors.lastname: Li
authors.forename: Kenji
authors.initials: K
authors.lastname: Kohno
authors.forename: Masahiko
authors.initials: M
authors.lastname: Hatano
authors.forename: Takeshi
authors.initials: T
authors.lastname: Tokuhisa
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Murray
authors.forename: Thomas
authors.initials: T
authors.lastname: Brocker
authors.forename: Moriya
authors.initials: M
authors.lastname: Tsuji
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005434:Flow Cytometry; D006183:H-2 Antigens / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D022781:Hepatocytes / Q000276:immunology / Q000378:metabolism; D007114:Immunization; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008288:Malaria / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D009842:Oligopeptides / Q000276:immunology; D010967:Plasmodium yoelii / Q000276:immunology / Q000378:metabolism; D015800:Protozoan Proteins / Q000276:immunology; D022223:Vaccines, Subunit / Q000276:immunology
chemical_list: D018984:Epitopes, T-Lymphocyte; D006183:H-2 Antigens; C024755:H-2K(K) antigen; D009842:Oligopeptides; D015800:Protozoan Proteins; D022223:Vaccines, Subunit; C041595:circumsporozoite protein, Protozoan; D007371:Interferon-gamma