Doherty T M, Bäckström B T, Prestidge R L, Love S G, Harding D R, Watson J D
Department of Molecular Medicine, School of Medicine, University of Auckland, New Zealand.
J Immunol. 1991 Mar 15;146(6):1934-40.
Antibody responses to the 18-kDa protein of Mycobacterium leprae have been analyzed in different strains of mice. High, intermediate, and low responder strains have been identified and these response patterns show clear linkage to genes encoded in the H-2 complex. Three peptides, residues 1-50, 51-100, and 101-148 have been synthesized, as well as a series of 20-mer peptides, which span the entire 18-kDa protein. Repeated immunization of different strains of mice with the 18-kDa protein resulted in IgG responses to epitopes found on all three synthetic peptides. Immunization of BALB/cJ and B10.BR mice, two high responder strains, with 18-kDa protein resulted in high levels of IgG antibody to epitopes found on peptides 1-20, 16-35, 31-50, 46-65, and 76-95. B10.BR mice also contained IgG that bound peptide 61-80 and BALB/cJ mice produced IgG that bound peptide 91-110. Although B10.BR mice produced IgG that bound the 50-mer peptide 101-148, this IgG was not detected by binding to peptides 91-110, 106-125, 121-140, and 131-148. Immunization of B10.BR mice with individual overlapping 20-mer peptides as Ag revealed that peptides 1-20, 16-35, 31-50, and 76-95 elicited high titers of IgG that bound both the immunizing peptide as well as 18-kDa protein. As these peptides induce antibody synthesis they must contain both B cell and T cell epitopes. By contrast, immunization of BALB/cJ mice with the same 20-mer peptides, all of which contain B cell epitopes for this strain, failed to elicit IgG responses with one exception. Peptide 91-110 induced IgG that bound peptide 91-110, but not the intact 18-kDa protein. We conclude that peptides 1-20, 16-35, 31-50, and 76-95 either lack T cell epitopes for BALB/cJ mice, or activate different T cell subpopulations in the two strains. We suggest that the induction of IgG responses to small peptide Ag is an in vivo assay of the activity of Th2 cell subpopulations.
已在不同品系的小鼠中分析了对麻风分枝杆菌18 kDa蛋白的抗体反应。已鉴定出高反应性、中等反应性和低反应性品系，这些反应模式与H-2复合体中编码的基因有明确的连锁关系。已合成了三个肽段，即第1 - 50位、第51 - 100位和第101 - 148位氨基酸残基的肽段，以及一系列覆盖整个18 kDa蛋白的20聚体肽段。用18 kDa蛋白反复免疫不同品系的小鼠，可诱导出针对所有三种合成肽段上抗原表位的IgG反应。用18 kDa蛋白免疫两种高反应性品系的BALB/cJ和B10.BR小鼠，可产生高水平的针对第1 - 20、16 - 35、31 - 50、46 - 65和76 - 95位氨基酸残基肽段上抗原表位的IgG抗体。B10.BR小鼠还含有能结合第61 - 80位氨基酸残基肽段的IgG，而BALB/cJ小鼠产生了能结合第91 - 110位氨基酸残基肽段的IgG。尽管B10.BR小鼠产生了能结合50聚体肽段第101 - 148位氨基酸残基的IgG，但通过与第91 - 110、106 - 125、121 - 140和131 - 148位氨基酸残基肽段结合未检测到这种IgG。用单个重叠的20聚体肽段作为抗原免疫B10.BR小鼠发现，第1 - 20、16 - 35、31 - 50和76 - 95位氨基酸残基肽段可诱导出高滴度的IgG，这些IgG既能结合免疫肽段，也能结合18 kDa蛋白。由于这些肽段可诱导抗体合成，它们必定同时含有B细胞和T细胞抗原表位。相比之下，用同样的20聚体肽段免疫BALB/cJ小鼠（所有这些肽段都含有该品系的B细胞抗原表位），除一个例外，均未能诱导出IgG反应。第91 - 110位氨基酸残基肽段诱导出的IgG能结合第91 - 110位氨基酸残基肽段，但不能结合完整的18 kDa蛋白。我们得出结论，第1 - 20、16 - 35、31 - 50和76 - 95位氨基酸残基肽段要么缺乏针对BALB/cJ小鼠的T细胞抗原表位，要么在这两个品系中激活了不同的T细胞亚群。我们认为，对小肽抗原诱导IgG反应是Th2细胞亚群活性的一种体内检测方法。
Zotero 插件