Identification of novel HLA-DR1-restricted epitopes from the hepatitis B virus envelope protein in mice expressing HLA-DR1 and vaccinated human subjects.
Helper T lymphocytes that control CD8(+) T-cell and antibody responses are key elements for the resolution of infection by the hepatitis B virus and for the development of effective immunological memory after hepatitis B vaccination. We have used H-2 class II-deficient mice that express the human MHC class II molecule, HLA-DR1, to identify novel hepatitis B virus envelope-derived T helper epitopes. We confirmed the immunogenicity of a previously described HLA-DR1-restricted epitope, and identified three novel epitopes. CD4(+) T-cell immune responses against these epitopes were detected in peripheral blood mononuclear cells from HLA-DR1(+) individuals vaccinated against hepatitis B. We showed that subjects receiving the currently available hepatitis B vaccines do not develop cross-reactive T helper responses against one of the novel epitopes which are structurally variable between different hepatitis B virus subtypes. These findings highlight the need for developing vaccines against a wider range of viral subtypes, and establish humanized mice as a convenient tool for identifying new immunogenic epitopes from pathogens.
Pajot
Anthony
A
Unité d'Immunité Cellulaire Antivirale, Département d'Immunologie, Institut Pasteur, 25-28 rue du Dr. Roux, 75015 Paris, France.
Michel
Marie-Louise
ML
Mancini-Bourgine
Maryline
M
Ungeheuer
Marie-Noelle
MN
Ojcius
David M
DM
Deng
Qiang
Q
Lemonnier
François A
FA
Lone
Yu-Chun
YC
D000293:Adolescent; D000328:Adult; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018604:Epitope Mapping; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D015798:HLA-DR1 Antigen / Q000235:genetics / Q000276:immunology*; D006509:Hepatitis B / Q000276:immunology*; D006514:Hepatitis B Surface Antigens / Q000276:immunology; D017325:Hepatitis B Vaccines / Q000276:immunology*; D006515:Hepatitis B virus / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation; D051379:Mice; D008822:Mice, Transgenic; D008875:Middle Aged; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D019444:Vaccines, DNA / Q000276:immunology; D014759:Viral Envelope Proteins / Q000276:immunology*
D018984:Epitopes, T-Lymphocyte; D015798:HLA-DR1 Antigen; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines; C118669:S envelope protein, hepatitis B virus; D019444:Vaccines, DNA; D014759:Viral Envelope Proteins