Vaccination of the Leishmania major susceptible BALB/c mouse. I. The precise selection of peptide determinant influences CD4+ T cell subset expression.
Vaccination of the Leishmania major susceptible BALB/c mouse. I. The precise selection of peptide determinant influences CD4+ T cell subset expression.
复制标题
利什曼原虫主要易感 BALB/c 小鼠的疫苗接种。
DOI：
10.1093/intimm/6.5.785
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发表时间：
1994
影响因子：
4.4
通讯作者：
Miller,A
中科院分区：
文献类型：
--
作者：
Soares,LR;Sercarz,EE;Miller,A
BALB/c小鼠感染主要利什曼原虫后对皮肤利什曼原虫敏感，而C57 BL/6小鼠则不敏感。存在一种主要的前鞭毛体表面蛋白酶（PSP或gp 63），其以天然和重组形式存在，并且其初级氨基酸序列是已知的。PSP的免疫接种已被证明可以提供一些保护，以抵御活生物体的挑战。因此，我们尝试用PSP肽开发肽疫苗。在第一个实验中，使用一组跨越整个PSP分子的15聚体肽测量对PSP的回忆促进反应，所述肽允许指定BALB/c、C57 BL/6和CBA小鼠中的主要决定簇区域。这些决定簇中有几个是混杂的，并且在不同菌株中共享几乎相同的核心氨基酸残基。主要决定簇肽免疫后，L.主要可溶性抗原以及PSP。如通过用于IFN-γ的单细胞产生的局部化ELISA测定所测量的，对肽的应答几乎完全是Th 1。IL-5的类似测定克服了Th 1细胞产生的淋巴因子的敏感性和抑制问题，表明即使BALB/c也很少产生Th 1细胞。结果发现，如果通过用重叠肽回忆来检查主要响应峰，则最高的中心肽主要产生Th 1响应，而边界的效率较低的肽产生更多的Th 2响应。讨论了可能的原因。这些结果指出了在考虑可能保护易感个体的疫苗原时选择精确合适的肽的重要性。甚至在决定簇包膜内选择某种免疫原性肽也可能通过将应答导向Th 2方向而实际上加剧感染。
BALB/c mice are susceptible to cutaneous lelshmanlasls upon infection withLeishmania majorwhile C57BL/6 are not. There is a major promastigote surface protease (PSP or gp63) which is available in both native and recomblnant forms, and for which the primary amlno acid sequence is known. Immunization with PSP has been shown to offer some protection against challenge with the live organism. Therefore, we attempted to develop a peptide vaccine with PSP peptldes. In the first experiments, recall prollferatlve responses to PSP were measured using a set of 15mer peptldes spanning the entire PSP molecule which allowed designation of major determinant regions in BALB/c, C57BL/6, and CBA mice. Several of these determinants were promiscuous and shared almost the identical core amlno acid residues in the different strains. Immunization with major determinant peptldes was recalled vigorously withL. majorsoluble antigen as well as with PSP. The response to peptide was almost entirely Th1 as measured by a localized ELISA assay for single-cell production of IFN-γ. A similar assay for IL-5, which overcomes problems of sensitivity and inhibition by lymphoklnes produced by Th1 cells, Indicates very little production of Th1 cells even by BALB/c. It was found that if a major responsive peak was examined by recall with overlapping peptldes, the highest, central peptide gave a mainly Th1 response while the boundary, less efficient peptldes gave more of a Th2 response. Possible reasons for this were discussed. These results point to the importance of selecting the exactly appropriate peptide in considering a vacclnogen that might protect susceptible individuals. Even the choice of a somewhat immunogenlc peptide within the determinant envelope might actually exacerbate infection by steering the response in a Th2 direction.