Induction of CTL response by a minimal epitope vaccine in HLA A*0201/DR1 transgenic mice: dependence on HLA class II restricted T(H) response

Hum Immunol. 2000 Aug;61(8):764-79. doi: 10.1016/s0198-8859(00)00139-7.


CTL play a pivotal role in the immune response during viral infections. In this study, the HLA class II restricted T(H) requirement for optimal in vivo induction of HLA class I restricted CTL responses has been investigated. Towards this goal, transgenic mice expressing both HLA class I (A*0201 or A2.1) and class II (DRB1*0101 or DR1) molecules have been derived. Immunization of these mice with an HLA A*0201-restricted and CMV-specific CTL epitope (pp65(495-503)), and either of three different tetanus toxin-derived MHC class II-binding T(H) epitopes, resulted in a vigorous CTL response. CTL specific for the pp65(495-503) epitope were dramatically enhanced in mice expressing both the HLA-DR1 and HLA-A*0201 transgenes. Notably, preinjection of three TT peptides (TT(639-652), TT(830-843), and TT(947-967)) increased the capability of HLA A*0201/DR1 Tg mice to respond to subsequent immunization with the T(H) + CTL peptide mixture. These results indicate that the use of HLA A*0201/DR1 Tg mice constitute a versatile model system (in lieu of immunizing humans) for the study of both HLA class I and class II restricted T-cell responses. These studies provide a rational model for the design and assessment of new minimal-epitope vaccines based on their in vivo induction of a pathogen-specific CTL response.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antigens, Viral / immunology
  • Cell Line
  • Cytomegalovirus / immunology
  • Epitopes, T-Lymphocyte / immunology*
  • HLA-A2 Antigen / genetics
  • HLA-A2 Antigen / immunology*
  • HLA-DR1 Antigen / genetics
  • HLA-DR1 Antigen / immunology*
  • Histocompatibility Antigens Class II / immunology*
  • Hypersensitivity, Delayed / immunology
  • Immunodominant Epitopes / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Molecular Sequence Data
  • Peptides / immunology
  • Phosphoproteins / immunology
  • T-Lymphocytes, Cytotoxic / immunology*
  • T-Lymphocytes, Helper-Inducer / immunology*
  • Tetanus Toxin / immunology
  • Viral Matrix Proteins / immunology
  • Viral Vaccines / immunology*


  • Antigens, Viral
  • Epitopes, T-Lymphocyte
  • HLA-A2 Antigen
  • HLA-DR1 Antigen
  • Histocompatibility Antigens Class II
  • Immunodominant Epitopes
  • Peptides
  • Phosphoproteins
  • Tetanus Toxin
  • Viral Matrix Proteins
  • Viral Vaccines
  • cytomegalovirus matrix protein 65kDa