: Major histocompatibility complex (MHC) presentation of peptides to cytotoxic T lymphocytes results in killing of infected cells. Thus assembly and peptide loading of MHC class I molecules is required to achieve cellular immune responses against infections. The binding of the MHC heavy chain to a peptide follows interactions with several endoplasmic reticulum (ER) proteins, such as calnexin, the transporter associated with antigen processing (TAP), calreticulin, tapasin, and ERp57. Recent studies have shown that amyloid precursor-like protein 2 (APLP-2) also associates with MHC class I molecules. We have found that APLP-2 down regulates the quantity of MHC class I molecules at the cell surface. Based on these preliminary findings, we hypothesize that APLP-2 regulates MHC class I maturation and presentation of peptides, including known epitopes from NIAID priority pathogens (Hantaan virus, Mycobacterium tuberculosis, influenza A virus, dengue virus, Japanese encephalitis virus, and Listeria monocytogenes). Results from these studies will clarify the role of APLP-2 in the MHC class I assembly pathway and may result in new means to prevent or treat infections.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32AI055152-02
Application #
6751968
Study Section
Special Emphasis Panel (ZRG1-F07 (20))
Program Officer
Prograis, Lawrence J
Project Start
2003-07-01
Project End
2006-06-30
Budget Start
2004-07-01
Budget End
2005-06-30
Support Year
2
Fiscal Year
2004
Total Cost
$48,928
Indirect Cost
Name
University of Nebraska Medical Center
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
168559177
City
Omaha
State
NE
Country
United States
Zip Code
68198
Lin, Xuede; Wang, Xiaojian; Capek, Haley L et al. (2009) Effect of invariant chain on major histocompatibility complex class I molecule expression and stability on human breast tumor cell lines. Cancer Immunol Immunother 58:729-36
Morris, Chantey R; Reber, Adrian J; Petersen, Jason L et al. (2004) Association of intracellular proteins with folded major histocompatibility complex class I molecules. Immunol Res 30:171-9