期刊
CANCER IMMUNOLOGY IMMUNOTHERAPY
卷 58, 期 9, 页码 1419-1431出版社
SPRINGER
DOI: 10.1007/s00262-009-0657-z
关键词
Amyloid precursor-like protein 2; Antigen presentation; Human leukocyte antigen; Major histocompatibility complex class I; Tumor
资金
- NIH [P30CA036727, GM57428, GM74876, T32 CA009476]
- Eppley Cancer Center Pediatric Cancer Research
- UNMC
- Nebraska Center for Cellular Signaling Fellowship
- American Heart Association Predoctoral Fellowship
- Graduate Assistance in Areas of National Need Fellowship
- NATIONAL CANCER INSTITUTE [P30CA036727, T32CA009476] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [R01GM057428, R01GM074876] Funding Source: NIH RePORTER
Amyloid precursor-like protein 2 (APLP2) is a ubiquitously expressed protein. The previously demonstrated functions for APLP2 include binding to the mouse major histocompatibility complex (MHC) class I molecule H-2K(d) and down regulating its cell surface expression. In this study, we have investigated the interaction of APLP2 with the human leukocyte antigen (HLA) class I molecule in human tumor cell lines. APLP2 was readily detected in pancreatic, breast, and prostate tumor lines, although it was found only in very low amounts in lymphoma cell lines. In a pancreatic tumor cell line, HLA class I was extensively co-localized with APLP2 in vesicular compartments following endocytosis of HLA class I molecules. In pancreatic, breast, and prostate tumor lines, APLP2 was bound to the HLA class I molecule. APLP2 was found to bind to HLA-A24, and more strongly to HLA-A2. Increased expression of APLP2 resulted in reduced surface expression of HLA-A2 and HLA-A24. Overall, these studies demonstrate that APLP2 binds to the HLA class I molecule, co-localizes with it in intracellular vesicles, and reduces the level of HLA class I molecule cell surface expression.
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