A mouse model of human adaptive immune functions: HLA-A2.1-/HLA-DR1-transgenic H-2 class I-/class II-knockout mice

Anthony Pajot, Marie Louise Michel, Nicolas Fazilleau, Véronique Pancré, Claude Auriault, David M. Ojcius, François A. Lemonnier, Yu Chun Lone*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

109 Scopus citations

Abstract

HLA-A2.1-/HLA-DR1-transgenic H-2 class I-/class II-knockout mice were created and their immunological potential evaluated in response to hepatitis B DNA vaccine. Every single immunized mouse developed hepatitis B virus-specific antibodies, HLA-DR1 -restricted helper, and HLA-A2.1 -restricted cytolytic T cell responses directed at the same immunodominant epitopes as those identified in naturally infected or vaccinated humans. These mice were specifically protected against a hepatitis B-recombinant vaccinia virus infection with a 10,000-fold or more reduction of the virus load at day 4 post-challenge. These mice represent a unique in vivo experimental model for human immune function studies without any interference with mouse MHC response which dwarfed the prediction of human responses. Furthermore, they enable the complete monitoring of immune adaptative responses for preclinical screening of candidate vaccines.

Original languageEnglish
Pages (from-to)3060-3069
Number of pages10
JournalEuropean Journal of Immunology
Volume34
Issue number11
DOIs
StatePublished - 11 2004
Externally publishedYes

Keywords

  • CTL/HTL
  • H-2 class I and II KO mice
  • HLA class I and II transgenic mice
  • Human immune response
  • Human vaccine evaluation

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