Noncovalent Association with Stress Protein Facilitates Cross-Priming of CD8+ T Cells to Tumor Cell Antigens by Dendritic Cells1
Noncovalent Association with Stress Protein Facilitates Cross-Priming of CD8+ T Cells to Tumor Cell Antigens by Dendritic Cells1
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与应激蛋白的非共价结合促进 CD8 T 细胞通过树突状细胞与肿瘤细胞抗原交叉引发1
作者：
R. Kammerer;D. Stober;Petra Riedl;C. Oehninger;R. Schirmbeck;J. Reimann
携带明确的Kb/Db限制性表位的病毒癌基因在小鼠肿瘤细胞P815和Meth-A中以热休克蛋白（hsp）相关或非相关形式表达。野生型SV 40大T-Ag（wtT-Ag）表达时无稳定的hsp结合;突变型（细胞质cT-Ag）或嵌合型（cT 272-绿色荧光融合蛋白）T-Ag表达时与组成型表达的细胞溶质hsp 73（hsc 70）蛋白稳定结合。在体外，来自凋亡的表达wtT-Ag或cT-Ag的肿瘤细胞的残余物被未成熟的树突状细胞（DC）摄取和加工，并且T-Ag的Kb/Db结合表位T1、T2/3和T4以TAP非依赖性方式交叉呈递给CTL。DC脉冲与残余的转染，凋亡的肿瘤细胞交叉提出的三个T-Ag表位更有效地处理ATP敏感的HSP 73/cT-Ag复合物时，比当他们处理HSP非相关的（本地）T-Ag。在体内，编码hsp 73结合突变T-Ag的DNA疫苗比编码天然非hsp结合T-Ag的DNA疫苗诱导更多的产生IFN-γ的CD 8 + T细胞。在F1（B × d）宿主中，转染H-2d Meth-A/cT肿瘤生长期间，T-Ag（T1-、T2/3-或T4-）特异性、DB/Kb限制性IFN-γ产生性CD 8 + T细胞的数量比转染Meth-A/T肿瘤生长期间高3 - 5倍。因此，癌基因与组成型表达的细胞溶质hsp 73的关联促进了DC处理来自凋亡细胞的材料在体外和体内对CTL的交叉引发。
A viral oncogene carrying well-defined Kb/Db-restricted epitopes was expressed in a heat shock protein (hsp)-associated or nonassociated form in the murine tumor cells P815 and Meth-A. Wild-type SV40 large T-Ag (wtT-Ag) is expressed without stable hsp association; mutant (cytoplasmic cT-Ag) or chimeric (cT272-green fluorescent fusion protein) T-Ag is expressed in stable association with the constitutively expressed, cytosolic hsp73 (hsc70) protein. In vitro, remnants from apoptotic wtT-Ag- or cT-Ag-expressing tumor cells are taken up and processed by immature dendritic cells (DC), and the Kb/Db-binding epitopes T1, T2/3, and T4 of the T-Ag are cross-presented to CTL in a TAP-independent way. DC pulsed with remnants of transfected, apoptotic tumor cells cross-presented the three T-Ag epitopes more efficiently when they processed ATP-sensitive hsp73/cT-Ag complexes than when they processed hsp-nonassociated (native) T-Ag. In vivo, more IFN-γ-producing CD8+ T cells were elicited by a DNA vaccine that encoded hsp73-binding mutant T-Ag than by a DNA vaccine that encoded native, non-hsp-binding T-Ag. Three- to 5-fold higher numbers of T-Ag (T1-, T2/3-, or T4-) specific, Db/Kb-restricted IFN-γ-producing CD8+ T cells were primed during the growth of transfected H-2d Meth-A/cT tumors than during the growth of transfected Meth-A/T tumors in F1(b × d) hosts. Hence, the association of an oncogene with constitutively expressed, cytosolic hsp73 facilitates cross-priming in vitro and in vivo of CTL by DC that process material from apoptotic cells.
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影响因子：
15.9
作者：
Fadok, VA;Bratton, DL;Henson, PM
通讯作者：
Henson, PM
DOI：
10.1073/pnas.90.7.3038
发表时间：
1993-04-01
影响因子：
11.1
作者：
INABA, K;INABA, M;STEINMAN, RM
通讯作者：
STEINMAN, RM
非胞质单核细胞增生李斯特氏菌分泌的抗原通过经典的 MHC I 类加工途径进行加工。
DOI：
--
发表时间：
1999
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Zwickey,HL;Potter,TA
通讯作者：
Potter,TA
细胞毒性 T 淋巴细胞逃逸变异、诱导突变和合成肽定义了猿病毒 40 肿瘤抗原中的显性 H-2Kb 限制性决定簇。
影响因子：
3.7
作者：
Mylin,LM;Deckhut,AM;Bonneau,RH;Kierstead,TD;Tevethia,MJ;Simmons,DT;Tevethi,SS
通讯作者：
Tevethi,SS
血小板活化因子和转化生长因子-β的自分泌/旁分泌参与诱导小鼠巨噬细胞识别磷脂酰丝氨酸。
DOI：
--
发表时间：
1995
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Rose,DM;Fadok,VA;Riches,DW;Clay,KL;Henson,PM
通讯作者：
Henson,PM