Wu T C, Guarnieri F G, Staveley-O'Carroll K F, Viscidi R P, Levitsky H I, Hedrick L, Cho K R, August J T, Pardoll D M
Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD 21287, USA.
Proc Natl Acad Sci U S A. 1995 Dec 5;92(25):11671-5. doi: 10.1073/pnas.92.25.11671.
The presentation of antigenic peptides by major histocompatibility complex (MHC) class II molecules to CD4+ T cells is critical to the function of the immune system. In this study, we have utilized the sorting signal of the lysosomal-associated membrane protein LAMP-1 to target a model antigen, human papillomavirus 16 E7 (HPV-16 E7), into the endosomal and lysosomal compartments. The LAMP-1 sorting signal reroutes the antigen into the MHC class II processing pathway, resulting in enhanced presentation to CD4+ cells in vitro. In vivo immunization experiments in mice demonstrated that vaccinia containing the chimeric E7/LAMP-1 gene generated greater E7-specific lymphoproliferative activity, antibody titers, and cytotoxic T-lymphocyte activities than vaccinia containing the wild-type HPV-16 E7 gene. These results suggest that specific targeting of an antigen to the endosomal and lysosomal compartments enhances MHC class II presentation and vaccine potency.
主要组织相容性复合体（MHC）II类分子将抗原肽呈递给CD4+ T细胞对免疫系统的功能至关重要。在本研究中，我们利用溶酶体相关膜蛋白LAMP-1的分选信号将模型抗原人乳头瘤病毒16 E7（HPV-16 E7）靶向至内体和溶酶体区室。LAMP-1分选信号将抗原重新导向MHC II类加工途径，从而在体外增强其向CD4+细胞的呈递。在小鼠体内进行的免疫实验表明，与含有野生型HPV-16 E7基因的痘苗病毒相比，含有嵌合E7/LAMP-1基因的痘苗病毒产生了更强的E7特异性淋巴细胞增殖活性、抗体滴度和细胞毒性T淋巴细胞活性。这些结果表明，将抗原特异性靶向至内体和溶酶体区室可增强MHC II类呈递和疫苗效力。
