Regulation of Antigen Presentation by APLP-2

University Of Nebraska Medical Center, Omaha NE

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Abstract

DESCRIPTION (provided by the applicant): 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.