Distinct and non-overlapping T cell receptor repertoires expanded by DNA vaccination in wild-type and HER-2 transgenic BALB/c mice
Distinct and non-overlapping T cell receptor repertoires expanded by DNA vaccination in wild-type and HER-2 transgenic BALB/c mice
复制标题
DOI：
10.4049/jimmunol.177.11.7626
复制
发表时间：
2006-12-01
影响因子：
4.4
通讯作者：
Ria, Francesco
中科院分区：
文献类型：
--
作者：
Rolla, Simona;Nicolo, Chiara;Ria, Francesco
对肿瘤相关AGS的中枢耐受是一种免疫逃逸机制，它显著限制了可用于肿瘤根除的TCR谱系。比较了野生型BALB/c和大鼠-HER-2/neu(rHER-2)转基因BALB-Neut小鼠在rHER-2 DNA免疫后扩增的谱带。每只小鼠使用一个或多个Vβ9-Jβ1.2片段的CD8(+)T细胞重排，其特征是CDR3的长度不同，并对63-71或1206-1214 rHER-2多肽具有特异性。此外，50%的小鼠体内出现了两次CD4(+)T细胞重排。相反，BALB-Neut小鼠对rHER-2表现出有限的反应。他们的曲目较小，并使用限于CD4(+)T细胞的不同重排。因此，BALB-Neut小鼠的中枢耐受通过沉默BALB/c小鼠的自身反应谱系和减少CD8(+)T细胞成分的大小来发挥作用。来自野生型和转基因小鼠的CD8(+)和CD4(+)T细胞。可获得的T细胞谱系的这一定义对于设计能够诱导针对HER-2驱动的致癌的有效免疫反应的免疫操作是至关重要的。免疫学杂志，2006,177：7626-7633。
Central tolerance to tumor-associated Ags is an immune-escape mechanism that significantly limits the TCR repertoires available for tumor eradication. The repertoires expanded in wild-type BALB/c and rat-HER-2/neu (rHER-2) transgenic BALB-neuT mice following DNA immunization against rHER-2 were compared by spectratyping the variable (V)beta and the joining (J)beta CDR 3. Following immunization, BALB/c mice raised a strong response. Every mouse used one or more CD8(+) T cell rearrangements of the V beta 9-J beta 1.2 segments characterized by distinct length of the CDR3 and specific for 63-71 or 1206-1214 rHER-2 peptides. In addition, two CD4(+) T cell rearrangements recurred in > 50% of mice. Instead, BALB-neuT mice displayed a limited response to rHER-2. Their repertoire is smaller and uses different rearrangements confined to CD4(+) T cells. Thus, central tolerance in BALB-neuT mice acts by silencing the BALB/c mice self-reactive repertoire and reducing the size of the CD8(+) T cell component. CD8(+) and CD4(+) T cells from both wild-type and transgenic mice home to tumors. This definition of the T cell repertoires available is critical to the designing of immunological maneuvers able to elicit an effective immune reaction against HER-2-driven carcinogenesis. The Journal of Immunology, 2006, 177: 7626-7633.