Different Vaccine Vectors Delivering the Same Antigen Elicit CD8+ T Cell Responses with Distinct Clonotype and Epitope Specificity
Different Vaccine Vectors Delivering the Same Antigen Elicit CD8+ T Cell Responses with Distinct Clonotype and Epitope Specificity
复制标题
DOI：
10.4049/jimmunol.0900581
复制
发表时间：
2009-08-15
影响因子：
4.4
通讯作者：
Nabel, Gary J.
中科院分区：
文献类型：
--
作者：
Honda, Mitsuo;Wang, Rui;Nabel, Gary J.
利用基因载体的初免-加强免疫已经被开发出来，以产生更有效的艾滋病、疟疾和结核病疫苗。虽然这些载体引起有效的T细胞应答，但它们刺激免疫的机制还不清楚。在这项研究中，我们表明，免疫的单一基因产品，HIV-1包膜，与替代载体组合eliminates CD 8（+）细胞具有不同的精细的特异性和动力学的动员。疫苗诱导的CD 8（+）T细胞识别重叠的第三V区环肽。出乎意料的是，两个锚变体比天然序列更好地结合H-2D（d），并且通过替代载体引发具有不同特异性的克隆。X射线晶体学揭示了MHC结合肽表位在溶剂暴露方面的重大差异，这表明加工的HIV-1包膜产生了被不同CD 8（+）T细胞群体识别的MHC-I/肽构象。这些发现表明，不同的基因为基础的载体产生的肽与替代构象内的MHC-I，引起不同的T细胞接种疫苗后的反应。免疫学杂志，2009，183：2425-2434.
Prime-boost immunization with gene-based vectors has been developed to generate more effective vaccines for AIDS, malaria, and tuberculosis. Although these vectors elicit potent T cell responses, the mechanisms by which they stimulate immunity are not well understood. In this study, we show that immunization by a single gene product, HIV-1 envelope, with alternative vector combinations elicits CD8(+) cells with different fine specificities and kinetics of mobilization. Vaccine-induced CD8(+) T cells recognized overlapping third V region loop peptides. Unexpectedly, two anchor variants bound H-2D(d) better than the native sequences, and clones with distinct specificities were elicited by alternative vectors. X-ray crystallography revealed major differences in solvent exposure of MHC-bound peptide epitopes, suggesting that processed HIV-1 envelope gave rise to MHC-I/peptide conformations recognized by distinct CD8(+) T cell populations. These findings suggest that different gene-based vectors generate peptides with alternative conformations within MHC-I that elicit distinct T cell responses after vaccination. The Journal of Immunology, 2009, 183: 2425-2434.