Honorati M C, Dolzani P, Mariani E, Piacentini A, Lisignoli G, Ferrari C, Facchini A
Laboratorio di Immunologia e Genetica, Istituto di Ricerca Codivilla Putti-Istituti Ortopedici Rizzoli, Bologna, Italy.
Gastroenterology. 1997 Jun;112(6):2017-27. doi: 10.1053/gast.1997.v112.pm9178695.
BACKGROUND & AIMS: Different amino acid sequences of hepatitis B virus surface antigen (HBsAg) are involved in the activation of CD4+ lymphocytes needed to induce an optimal antiviral function. The aim of this study was to characterize the CD4-mediated response to immunodominant HBsAg epitopes in hepatitis B virus (HBV) vaccine recipients by defining minimal sequences recognized by T cells, cytokine profiles, and HLA restriction of peptide recognition.
T-lymphocyte lines and clones specific for HBsAg were isolated from the peripheral blood of subjects immunized with recombinant HBsAg and stimulated in vitro with synthetic peptides spanning the whole HBsAg sequence.
Four immunodominant epitopes (sequences 21-40, 136-155, 156-175, and 211-226) were identified. Using panels of truncated peptides of different length, sequences 21-28, 165-172, and 215-223 were shown to correspond to the minimal epitopes recognized by T cells. The antigen-specific T-lymphocyte proliferation was HLA class II restricted, and each peptide could be presented in association with different HLA class II determinants. Th0/Th2 cytokine patterns were induced on peptide stimulation.
These results indicate the presence of at least four immunodominant epitopes within HBsAg that represent potential candidates for the design of anti-HBV synthetic vaccines.
乙肝病毒表面抗原（HBsAg）的不同氨基酸序列参与诱导最佳抗病毒功能所需的CD4+淋巴细胞的激活。本研究的目的是通过确定T细胞识别的最小序列、细胞因子谱以及肽识别的HLA限制，来表征乙肝病毒（HBV）疫苗接种者中CD4介导的对免疫显性HBsAg表位的反应。
从用重组HBsAg免疫的受试者外周血中分离出对HBsAg特异的T淋巴细胞系和克隆，并在体外用人造肽刺激，这些人造肽覆盖整个HBsAg序列。
鉴定出四个免疫显性表位（序列21 - 40、136 - 155、156 - 175和211 - 226）。使用不同长度截短肽组，显示序列21 - 28、165 - 172和215 - 223对应于T细胞识别的最小表位。抗原特异性T淋巴细胞增殖受HLA II类限制，每个肽可与不同的HLA II类决定簇呈递。肽刺激诱导Th0/Th2细胞因子模式。
这些结果表明HBsAg内存在至少四个免疫显性表位，它们是设计抗HBV合成疫苗的潜在候选物。
