CD13 regulates dendritic cell cross-presentation and T cell responses by inhibiting receptor-mediated antigen uptake.
CD13 regulates dendritic cell cross-presentation and T cell responses by inhibiting receptor-mediated antigen uptake.
复制标题
DOI：
10.4049/jimmunol.1103490
复制
发表时间：
2012-06-01
期刊：
影响因子：
--
通讯作者：
Shapiro LH
中科院分区：
文献类型：
--
作者：
Ghosh M;McAuliffe B;Subramani J;Basu S;Shapiro LH
树突状细胞（DC）抗原交叉呈递通常与针对肿瘤和病毒抗原的免疫应答相关，并且增强该过程是肿瘤疫苗设计的焦点。在这项研究中，我们发现，髓系细胞表面肽酶CD13是高度和特异性表达的DC负责交叉呈递的子集，CD8+小鼠脾脏DC。在体内研究表明，缺乏CD13显着增强T细胞对可溶性OVA抗原的反应，虽然DC的发育，成熟，抗原加工和呈递在CD13 KO小鼠中是正常的。体外研究表明，CD13调节受体介导的、动力蛋白依赖的抗原内吞作用，如OVA和转铁蛋白，但不调节液相或吞噬细胞的抗原摄取。CD13和抗原在DC中共内化，但CD13不与抗原受体共免疫沉淀，表明CD13不控制特异性受体的内化，但在更普遍的水平上调节内吞作用。从机制上讲，我们发现CD 13 KO DC中内吞调节因子p38 MAPK和Akt的磷酸化失调，阻断这些激酶会扰乱CD 13依赖性内吞摄取。因此，CD13是一种新型的内吞调节因子，可用于增强抗原摄取和T细胞活化，以提高肿瘤靶向疫苗的功效。
Dendritic cell (DC) antigen cross-presentation is generally associated with immune responses to tumors and viral antigens and enhancing this process is a focus of tumor vaccine design. In this study, we found that the myeloid cell surface peptidase CD13 is highly and specifically expressed on the subset of DCs responsible for cross-presentation, the CD8+ murine splenic DCs. In vivo studies indicated that lack of CD13 significantly enhanced T cell responses to soluble OVA antigen, although development, maturation, antigen processing and presentation of DCs are normal in CD13KO mice. In vitro studies showed that CD13 regulates receptor-mediated, dynamin-dependent endocytosis of antigens such as OVA and transferrin but not fluid-phase or phagocytic antigen uptake. CD13 and antigen are co-internalized in DCs but CD13 did not co-immunoprecipitate with antigen receptors, suggesting that CD13 does not control internalization of specific receptors but regulates endocytosis at a more universal level. Mechanistically, we found that phosphorylation of the endocytic regulators p38MAPK and Akt was dysregulated in CD13KO DCs and blocking these kinases perturbed CD13-dependent endocytic uptake. Therefore, CD13 is a novel endocytic regulator that may be exploited to enhance antigen uptake and T cell activation to improve the efficacy of tumor-targeted vaccines.
登录
查看更多内容
影响因子：
2.8
作者：
Gabrilovac, Jelka;Cupic, Barbara;Majhen, Dragomira
通讯作者：
Majhen, Dragomira
影响因子：
4.4
作者：
Burgdorf, Sven;Lukacs-Kornek, Veronika;Kurts, Christian
通讯作者：
Kurts, Christian
DOI：
10.1073/pnas.88.9.3972
发表时间：
1991-05-01
影响因子：
11.1
作者：
KARTTUNEN, J;SHASTRI, N
通讯作者：
SHASTRI, N
DOI：
10.1084/jem.192.12.1685
发表时间：
2000-12-18
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
den Haan JM;Lehar SM;Bevan MJ
通讯作者：
Bevan MJ
影响因子：
3.3
作者：
Ait-Slimane, Tounsia;Galmes, Romain;Maurice, Michele
通讯作者：
Maurice, Michele