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Characterization of a conserved helper-T-cell epitope from group A Streptococcal M proteins.

机译:A组链球菌M蛋白保守的辅助T细胞表位的表征。

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We have previously defined major histocompatibility complex (MHC) class II-restricted T-cell epitopes from the carboxy-terminal region of group A streptococcal type 5 M protein. In this report, T-cell responses to one of these epitopes have been characterized in detail. T-cell clones from recombinant M5-immunized mice and popliteal lymph node cells from peptide-immunized mice were used to show that sM5[300-319] is recognized in the context of I-A alleles of four of nine independent MHC class II haplotypes: I-Ad, I-Af, I-Ak, and I-As. This epitope was also recognized by both helper (Th2) and inflammatory (Th1) subsets of murine T cells. The I-Ad-restricted epitope recognized by BALB/c mice was mapped to the 12-amino-acid peptide sM5[308-319] and was shown to provide helper function for an immunoglobulin G anti-peptide antibody response in BALB/c mice. Anti-peptide antibody was shown to be specific for M5[304-315] but failed to recognize intact rM5, suggesting that the conformation of the epitope differed between peptide and protein. However, the results demonstrate that overlapping epitopes can be the focus for both immunoglobulin G antibodies and the T cells which augment their production. Comparison of the available sequences for M proteins indicated that the T-cell epitope within M5[300-319] was highly conserved between M types and hence may elicit helper function for protective antibody responses to a wide range of M types. T-cell epitopes from conserved regions of M proteins which are recognized in the context of multiple MHC haplotypes have potential for the design of multivalent streptococcal vaccines.
机译:我们以前从A组链球菌5 M型蛋白的羧基末端区域定义了主要的组织相容性复合物(MHC)II类限制性T细胞表位。在此报告中,已详细描述了对这些表位之一的T细胞反应。重组M5免疫小鼠的T细胞克隆和肽免疫小鼠的pop淋巴结细胞用于显示sM5 [300-319]在9个独立的MHC II类单倍型中的四个的IA等位基因中被识别: -Ad,I-Af,I-Ak和I-As。该表位也被鼠T细胞的辅助(Th2)和炎性(Th1)亚型识别。被BALB / c小鼠识别的I-Ad限制性表位被定位到12个氨基酸的肽sM5 [308-319],并被证明为BALB / c小鼠的免疫球蛋白G抗肽抗体应答提供辅助功能。已显示抗肽抗体对M5具有特异性[304-315],但无法识别完整的rM5,这表明表位的构象在肽和蛋白质之间有所不同。然而,结果表明,重叠的表位可能是免疫球蛋白G抗体和增加其产量的T细胞的焦点。 M蛋白可用序列的比较表明,M5之间的M5 [300-319]中的T细胞表位是高度保守的,因此可能引发针对多种M型保护性抗体的辅助功能。在多种MHC单倍型的背景下识别的M蛋白保守区的T细胞表位具有设计多价链球菌疫苗的潜力。

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