Generation of tissue-specific H-2Kd transgenic mice for the study of K(d)-restricted malaria epitope-specific CD8+ T-cell responses in vivo

J Immunol Methods. 2013 Jan 31;387(1-2):254-61. doi: 10.1016/j.jim.2012.10.019. Epub 2012 Nov 8.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antigen-Presenting Cells / immunology
  • Antigen-Presenting Cells / metabolism
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Epitopes, T-Lymphocyte / immunology*
  • Flow Cytometry
  • H-2 Antigens / genetics
  • H-2 Antigens / immunology*
  • H-2 Antigens / metabolism
  • Hepatocytes / immunology
  • Hepatocytes / metabolism
  • Immunization
  • Interferon-gamma / immunology
  • Interferon-gamma / metabolism
  • Macrophages / immunology
  • Macrophages / metabolism
  • Malaria / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Microscopy, Fluorescence
  • Oligopeptides / immunology
  • Plasmodium yoelii / immunology
  • Plasmodium yoelii / metabolism
  • Protozoan Proteins / immunology
  • Vaccines, Subunit / immunology


  • Epitopes, T-Lymphocyte
  • H-2 Antigens
  • H-2K(K) antigen
  • Oligopeptides
  • Protozoan Proteins
  • Vaccines, Subunit
  • circumsporozoite protein, Protozoan
  • Interferon-gamma