H-2 class I knockout, HLA-A2.1-transgenic mice: a versatile animal model for preclinical evaluation of antitumor immunotherapeutic strategies

Eur J Immunol. 1999 Oct;29(10):3112-21. doi: 10.1002/(SICI)1521-4141(199910)29:10<3112::AID-IMMU3112>3.0.CO;2-Q.


H-2 class I-negative, HLA-A2.1-transgenic HHD mice were used for a comparative evaluation of the immunogenicity of HLA-A2.1-restricted human tumor-associated cytotoxic T lymphocyte (CTL) epitopes. A hierarchy was established among these peptides injected into mice in incomplete Freund's adjuvant which correlates globally with their capacity to bind and stabilize HLA-A2.1 molecules. Co-injection of a helper peptide enhanced most CTL responses. In contrast, classical HLA class I-transgenic mice which still express their own class I molecules did not, in most cases, develop HLA-A2.1-restricted CTL responses under the same experimental conditions. Different monoepitope immunization strategies of acceptable clinical usage were compared in HHD mice. Recombinant Ty-virus-like particles, or DNA encoding epitopes fused to the hepatitis B virus middle envelope protein gave the best results. Using this latter approach and a melanoma-based polyepitope construct, CTL responses against five distinct epitopes could be elicited simultaneously in a single animal. Thus, HHD mice provide a versatile animal model for preclinical evaluation of peptide-based cancer immunotherapy.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • CD8 Antigens / immunology
  • CD8 Antigens / therapeutic use
  • Cancer Vaccines / genetics*
  • Cancer Vaccines / immunology*
  • Disease Models, Animal*
  • Epitopes, T-Lymphocyte / immunology
  • H-2 Antigens / genetics*
  • H-2 Antigens / immunology
  • HLA-A2 Antigen / genetics*
  • HLA-A2 Antigen / immunology
  • HLA-A2 Antigen / metabolism
  • Hepatitis B Core Antigens / immunology
  • Humans
  • Immunodominant Epitopes / immunology
  • Immunodominant Epitopes / therapeutic use
  • Immunotherapy, Active / methods*
  • Melanoma / immunology
  • Melanoma, Experimental / genetics
  • Melanoma, Experimental / immunology*
  • Melanoma, Experimental / therapy*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Molecular Sequence Data
  • Peptides / immunology
  • Peptides / therapeutic use


  • CD8 Antigens
  • Cancer Vaccines
  • Epitopes, T-Lymphocyte
  • H-2 Antigens
  • HLA-A2 Antigen
  • Hepatitis B Core Antigens
  • Immunodominant Epitopes
  • Peptides