Molecular mimicry of hepatitis B surface antigen by an anti-idiotype-derived synthetic peptide.

Monoclonal antibody 2F10 is an "internal-image" anti-idiotype (anti-id) antibody capable of mimicking the group-specific "a" determinant of human hepatitis B surface antigen (HBsAg). By mRNA sequencing and computer-assisted molecular modeling of monoclonal antibody 2F10, we identified a 15-amino acid region of the heavy-chain hypervariable region that has partial residue homology with sequences of the "a" determinant epitopes of HBsAg. We have established that a linear 15-mer peptide from a contiguous region on the anti-id antibody can (i) generate anti-HBsAg-specific antibodies when injected into mice, (ii) prime murine lymph node cells for in vitro HBsAg-specific T-cell proliferative responses, and (iii) stimulate in vitro human CD4+ T cells that were primed in vivo to HBsAg by natural infection with hepatitis B virus or vaccination with a commercially available HBsAg vaccine. Significantly, this peptide could also stimulate CD4+ T cells of human hepatitis B virus carriers. We conclude that a 15-mer peptide derived from the anti-id sequence can duplicate the B- and T-cell stimulatory activity of the intact anti-id antibody and the antigen that is mimicked, HBsAg. IMAGES:

单克隆抗体2F10是一种内影像抗独特型（anti-id）抗体，可模拟人类乙型肝炎病毒表面抗原（HBsAg）的群特异性“a”决定簇。通过对单克隆抗体2F10开展mRNA测序与计算机辅助分子建模，我们鉴定出其重链高变区中的一段15氨基酸区域，该区域的残基与HBsAg“a”决定簇表位序列存在部分同源性。我们证实，取自该抗独特型抗体连续区域的线性15肽可实现如下功能：(i) 注入小鼠体内后可诱导产生抗HBsAg特异性抗体；(ii) 致敏小鼠淋巴结细胞，使其在体外产生HBsAg特异性T细胞增殖反应；(iii) 在体外刺激因自然感染乙型肝炎病毒或接种商用HBsAg疫苗而在体内预先致敏的人类CD4+ T细胞。尤为重要的是，该肽还可刺激乙型肝炎病毒携带者的CD4+ T细胞。我们得出结论：源自该抗独特型抗体序列的15肽，可复现完整抗独特型抗体及其所模拟的抗原HBsAg的B细胞与T细胞刺激活性。IMAGES: