Amyloid precursor-like protein 2 association with HLA class I molecules
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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-2Kd 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.
KeywordsAmyloid precursor-like protein 2 Antigen presentation Human leukocyte antigen Major histocompatibility complex class I Tumor
We thank Dr. Shantaram Joshi, Dr. Kenneth Cowan, Dr. Vinod Labhasetwar, Dr. Michael A. Hollingsworth, Dr. Richard MacDonald, Dr. John Chan, Vivek Gautam, Christopher Connelly, Michelle Hartman, Himabindu Ramachandrareddy, Jaspreet Vasir, Tom Caffrey, Dr. Pankaj Singh, Dr. Wendy Maury, and Dr. Ted Hansen for their assistance with obtaining cell lines and antibodies, and we thank Dr. Atsunori Hiasa and Dr. Hiroshi Shiku for the HLA-A*2404 cDNA. We gratefully acknowledge the assistance of the personnel of the UNMC Cell Analysis Facility and the Monoclonal Antibody Facility. Core facilities at UNMC receive support from the NIH Cancer Center Support Grant P30CA036727. This work was supported by NIH Grants GM57428 (to J.C.S.) and GM74876 (to S.C.), an Eppley Cancer Center Pediatric Cancer Research Grant, UNMC Graduate Studies Fellowships (to A.T., M.S., and L.S.), a Nebraska Center for Cellular Signaling Fellowship and an American Heart Association Predoctoral Fellowship (to M.S.), an NIH Training Grant T32 CA009476 Fellowship (to L.S.), and a Graduate Assistance in Areas of National Need Fellowship (to H.C.).
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