Pruksakorn S, Galbraith A, Houghten R A, Good M F
Molecular Immunology Unit, Queensland Institute of Medical Research, Brisbane, Australia.
J Immunol. 1992 Oct 15;149(8):2729-35.
To identify conserved T and B cell epitopes on the M protein of group A beta-hemolytic streptococci, overlapping synthetic peptides that span the conserved carboxyl-terminal segment of the M-5 protein were constructed and used to immunize a panel of H-2 congenic mice. Proliferative T cell epitopes were identified and, in many cases, mice immunized with these peptides produced high titer antibodies to the same peptides indicating that these proliferative epitopes could also stimulate Th cells. Peptide-specific T cells and antisera were tested for their reactivity with porcine myosin, tropomyosin, human heart myosin synthetic peptides, and extracts of human pericardial and atrial heart tissue. Although there was minimal response of M peptide-specific T cells to any of these Ag, certain M peptide-specific antisera reacted to immunoblotted porcine myosin and to an immunoblotted extract of human atrial heart tissue. However, two conserved peptides, LRRDLDASREAKKQVEKALE and KLTEKEKAELQAKLEAEAKA, stimulated peptide-specific antibodies in B10.BR and B10.D2 mice respectively, which reacted minimally if at all with human atrial heart tissue extract. Furthermore, antisera to the former peptide, in a bactericidal assay involving human monocytes, could mediate killing of streptococci (82% of bacteria). Although this level of killing is less than that produced by antisera to the highly polymorphic type-specific aminoterminus (up to 100% killing), it provides evidence that conserved epitopes can be the targets of bactericidal antibodies. These conserved epitopes may be useful in a vaccine because they also stimulate T cells, thus allowing development of immunologic memory and natural boosting of an immune response after natural exposure.
为了鉴定 A 组β溶血性链球菌 M 蛋白上保守的 T 细胞和 B 细胞表位，构建了跨越 M-5 蛋白保守羧基末端片段的重叠合成肽，并用于免疫一组 H-2 同基因小鼠。确定了增殖性 T 细胞表位，在许多情况下，用这些肽免疫的小鼠产生了针对相同肽的高滴度抗体，这表明这些增殖性表位也能刺激 Th 细胞。测试了肽特异性 T 细胞和抗血清与猪肌球蛋白、原肌球蛋白、人心脏肌球蛋白合成肽以及人心包和心房心脏组织提取物的反应性。尽管 M 肽特异性 T 细胞对任何这些抗原的反应极小，但某些 M 肽特异性抗血清与免疫印迹的猪肌球蛋白和人心房心脏组织的免疫印迹提取物发生反应。然而，两个保守肽，LRRDLDASREAKKQVEKALE 和 KLTEKEKAELQAKLEAEAKA，分别在 B10.BR 和 B10.D2 小鼠中刺激了肽特异性抗体，这些抗体与人心房心脏组织提取物的反应极小或根本没有反应。此外，在涉及人单核细胞的杀菌试验中，针对前一种肽的抗血清可以介导链球菌的杀伤（82%的细菌）。尽管这种杀伤水平低于针对高度多态性的型特异性氨基末端的抗血清所产生的杀伤水平（高达 100%的杀伤），但它提供了证据表明保守表位可以成为杀菌抗体的靶点。这些保守表位可能在疫苗中有用，因为它们也能刺激 T 细胞，从而允许免疫记忆的发展以及自然暴露后免疫反应的自然增强。
