Amyloid precursor-like protein 2 association with HLA class i molecules

Amit Tuli, Mahak Sharma, Xiaojian Wang, Laura C. Simone, Haley L. Capek, Steven Cate, William H. Hildebrand, Naava Naslavsky, Steve Caplan, Joyce C. Solheim

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1419-1431
Number of pages13
JournalCancer Immunology, Immunotherapy
Volume58
Issue number9
DOIs
StatePublished - Sep 2009

Keywords

  • Amyloid precursor-like protein 2
  • Antigen presentation
  • Human leukocyte antigen
  • Major histocompatibility complex class I
  • Tumor

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology
  • Cancer Research

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