Derivation of HLA-B*0702 transgenic mice: functional CTL repertoire and recognition of human B*0702-restricted CTL epitopes

Hum Immunol. 2003 Feb;64(2):211-23. doi: 10.1016/s0198-8859(02)00786-3.


Transgenic mice expressing chimeric human leukocyte antigen (HLA)-B*0702 and murine H-2K(b) class I molecules were evaluated as a model system to study the immunogenicity of human cytotoxic T lymphocyte epitopes. Immunization of these mice with six known HLA-B*0702-restricted cytotoxic T lymphocyte epitopes emulsified in incomplete Freund's adjuvant induced significant immune responses specific for all six epitopes. A comparison of the immune responses between HLA-B*0702/K(b) and HLA-A*0201/K(b) transgenic mice demonstrated that the HLA-B*0702/K(b) mice possess a T-cell receptor repertoire capable of recognizing human B*0702 epitopes. However, the magnitude of B*0702-specific responses induced in B*0702/K(b) mice were approximately tenfold lower than A*0201-specific responses induced in HLA-A*0201/K(b) transgenic mice. A panel of 24 B*0702 motif-bearing peptides was used to examine the relationship between immunogenicity and HLA-B*0702 binding capacity. All seven peptides with high binding affinities of 50% inhibitory concentration < or =50 NM (IC(50) 50 nM or less) were immunogenic. Similarly, 75% (9 of 12) of the intermediate binders (IC(50) nM of 50-500) were also immunogenic. Finally, only two of five peptides with binding capacity > 500 nM were found to have marginal immunogenicity, whereas the other three were completely negative. HLA-B*0702/K(b) transgenic mice were found to induce B*0702-specific responses after immunization with whole DNA genes or minigenes, suggesting that, at least to some degree, B*0702 epitopes were generated as a result of natural in vivo processing and presentation.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antigen Presentation
  • Cell Line
  • Cytotoxicity, Immunologic
  • Epitopes, T-Lymphocyte / immunology*
  • Genes, MHC Class I
  • Genes, Synthetic
  • H-2 Antigens / genetics
  • H-2 Antigens / immunology
  • HLA-A Antigens / genetics
  • HLA-A Antigens / immunology
  • HLA-A2 Antigen
  • HLA-B Antigens / genetics*
  • HLA-B Antigens / immunology
  • HLA-B7 Antigen
  • Humans
  • Immunization
  • Immunodominant Epitopes / immunology
  • Interferon-gamma / metabolism
  • Jurkat Cells
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Molecular Sequence Data
  • Peptide Fragments / immunology
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / immunology
  • T-Lymphocytes, Cytotoxic / immunology*


  • Epitopes, T-Lymphocyte
  • H-2 Antigens
  • H-2Kb protein, mouse
  • HLA-A Antigens
  • HLA-A*02:01 antigen
  • HLA-A2 Antigen
  • HLA-B Antigens
  • HLA-B*07:02 antigen
  • HLA-B7 Antigen
  • Immunodominant Epitopes
  • Peptide Fragments
  • Recombinant Fusion Proteins
  • Interferon-gamma