Use of transgenic HLA A*0201/Kb and HHD II mice to evaluate frequency of cytomegalovirus IE1-derived peptide usage in eliciting human CD8 cytokine response

J Virol. 2003 Apr;77(7):4457-62. doi: 10.1128/jvi.77.7.4457-4462.2003.

Abstract

Unlike the pp65 protein of human cytomegalovirus (CMV), which has an immunodominant peptide, pp65(495-503), recognized by human CD8(+) cells in the context of HLA A*0201, the fine peptide specificity for CMV IE1 has shown no such immunodominance. With the use of transgenic HLA A*0201/Kb and HHD II mice, a selected pool of IE1 peptides, including IE1(p256-264), IE1(p297-304), and IE1(p316-324), were shown to stimulate cytolytic T-lymphocyte lysis in the context of HLA A*0201. Based on an intracellular gamma interferon response, IE1(p297-304), a previously unrecognized CD8 epitope, triggered a prominent response to CMV IE1 in HLA A*0201 subjects.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • CD8-Positive T-Lymphocytes / immunology*
  • Cytomegalovirus / genetics
  • Cytomegalovirus / immunology*
  • Cytomegalovirus Infections / immunology
  • Granulocyte-Macrophage Colony-Stimulating Factor / administration & dosage
  • Granulocyte-Macrophage Colony-Stimulating Factor / genetics
  • HLA-A Antigens / genetics*
  • HLA-A2 Antigen
  • Humans
  • Immediate-Early Proteins / genetics
  • Immediate-Early Proteins / immunology*
  • Immunodominant Epitopes / genetics
  • In Vitro Techniques
  • Interferon-gamma / biosynthesis
  • Mice
  • Mice, Transgenic
  • Peptide Fragments / genetics
  • Peptide Fragments / immunology
  • Phosphoproteins / administration & dosage
  • Phosphoproteins / genetics
  • Recombinant Proteins
  • T-Lymphocytes, Cytotoxic / immunology
  • Vaccines, DNA / administration & dosage
  • Vaccines, DNA / genetics
  • Viral Matrix Proteins / administration & dosage
  • Viral Matrix Proteins / genetics
  • Viral Proteins*
  • Viral Vaccines / administration & dosage
  • Viral Vaccines / genetics

Substances

  • HLA-A Antigens
  • HLA-A*02:01 antigen
  • HLA-A2 Antigen
  • IE1 protein, cytomegalovirus
  • Immediate-Early Proteins
  • Immunodominant Epitopes
  • Peptide Fragments
  • Phosphoproteins
  • Recombinant Proteins
  • Vaccines, DNA
  • Viral Matrix Proteins
  • Viral Proteins
  • Viral Vaccines
  • cytomegalovirus matrix protein 65kDa
  • Interferon-gamma
  • Granulocyte-Macrophage Colony-Stimulating Factor