Pajot Anthony, Michel Marie-Louise, Mancini-Bourgine Maryline, Ungeheuer Marie-Noelle, Ojcius David M, Deng Qiang, Lemonnier François A, Lone Yu-Chun
Unité d'Immunité Cellulaire Antivirale, Département d'Immunologie, Institut Pasteur, 25-28 rue du Dr. Roux, 75015 Paris, France.
Microbes Infect. 2006 Oct;8(12-13):2783-90. doi: 10.1016/j.micinf.2006.08.009. Epub 2006 Sep 12.
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.
控制CD8(+) T细胞和抗体反应的辅助性T淋巴细胞是解决乙型肝炎病毒感染以及乙型肝炎疫苗接种后产生有效免疫记忆的关键因素。我们使用了表达人类MHC II类分子HLA-DR1的H-2 II类缺陷小鼠来鉴定新型乙型肝炎病毒包膜衍生的T辅助表位。我们证实了先前描述的HLA-DR1限制性表位的免疫原性，并鉴定出三个新表位。在接种乙型肝炎疫苗的HLA-DR1(+)个体的外周血单核细胞中检测到针对这些表位的CD4(+) T细胞免疫反应。我们发现，接受目前可用的乙型肝炎疫苗的受试者不会产生针对其中一个新表位的交叉反应性T辅助反应，该表位在不同乙型肝炎病毒亚型之间结构可变。这些发现凸显了开发针对更广泛病毒亚型的疫苗的必要性，并确立了人源化小鼠作为从病原体中鉴定新免疫原性表位的便捷工具。
