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首页> 外文期刊>International Journal of Peptide Research and Therapeutics >Assessment of Human Immune Response to Mutans Streptococcal Glucosyltransferase Peptides Selected by MHC Class II Binding Probability
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Assessment of Human Immune Response to Mutans Streptococcal Glucosyltransferase Peptides Selected by MHC Class II Binding Probability

机译：评估人类对MHC II类结合概率选择的变形链球菌葡萄糖转移酶肽的免疫反应

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摘要

Dental decay is a major public health challenge, causing substantial social and economic burdens. In animals, vaccination against mutans streptococci, the causative organism, interferes with dental caries. The mutans streptococcal glucosyltransferase (GTF) has been effectively used as a protein antigen in experimental dental caries vaccines. Compared to whole proteins, peptide subunits can focus immune responses on protective epitopes, and not on potentially harmful cross reactive antigens. In the past we selected peptide subunits of GTF for vaccine discovery based on putative functional significance and conservation of GTF primary structure. To focus on the immunogenicity of peptides, we estimated the probability of MHC class II binding. Twenty 20-mer linear GTF peptides were synthesized on this basis and their immunoreactivity explored. Significant human peripheral blood mononuclear cell (PBMC; n = 12) proliferation was observed in response to amino acids (AA) 502–521 (peptide 7), located in the catalytic domain of GTF. Human serum (n = 36) antibody reactivity was observed to AA 438–457 (peptide 5), AA 502–521 (peptide 7), and AA 1376–1395 (peptide 16). Whole saliva mutans streptococcal levels were used as markers of mutans infection, and dental examinations to determine existing and historic caries (DMFS score) were performed. DMFS scores correlated with mutans streptococcal counts, but not with immune responses. We have identified peptides with projected avid MHC-binding activity that reacted with human PBMC and serum antibody, implying that these peptides are immunogenic and may be of significance in a subunit dental caries vaccine.
机译：龋齿是一项重大的公共卫生挑战，给社会和经济造成沉重负担。在动物中，针对致病性生物体变形链球菌的疫苗接种会干扰龋齿。变形链球菌葡糖基转移酶（GTF）已有效用作实验性龋齿疫苗中的蛋白质抗原。与完整蛋白相比，肽亚基可以将免疫反应集中在保护性表位上，而不是潜在有害的交叉反应性抗原上。过去，我们基于推定的功能意义和GTF一级结构的保守性，选择了GTF的肽亚基进行疫苗发现。为了专注于肽的免疫原性，我们估计了II类MHC结合的可能性。在此基础上合成了20个20-mer线性GTF肽，并探讨了其免疫反应性。响应于位于GTF催化域中的氨基酸（AA）502-521（7号肽），观察到人类外周血单个核细胞（PBMC； n = 12）明显增殖。观察到人血清（n = 36）对AA 438-457（肽5），AA 502-521（肽7）和A 1376-1395（肽16）具有抗体反应性。唾液中的全部变形链球菌水平被用作变形菌感染的标志物，并进行了牙科检查以确定现有和历史龋齿（DMFS评分）。 DMFS评分与变形链球菌计数相关，但与免疫反应无关。我们已经鉴定出具有预测的与人PBMC和血清抗体反应的抗MHC结合活性的肽，这暗示这些肽具有免疫原性，在亚基龋齿疫苗中可能具有重要意义。

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