The Journal of Immunology, 2007, 178: 93.2.
Copyright © 2007 by The American Association of Immunologists, Inc.
Viral and Self HLA Class I Peptides Mark the Surface of Influenza Infected Cells
Angela Raquel Wahl1,
Fredda Schafer1,
Wilfried Bardet1,
Rico Buchli1,
Malaroviyam Samikkannu1,
Annette Fleshman1,
Melva Gonzalez1,
Gillian Air2 and
William Hildebrand1
1 Microbiology and Immunology, University of Oklahoma Health Sciences Center, 975 NE 10th Street, BRC 317, Oklahoma City, Oklahoma, 73104,
2 Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, 940 S. L. Young Blvd., BMSB 840A, Oklahoma City, Oklahoma, 73104
Abstract
The influenza virus attacks epithelial cells of the lower and upper respiratory tracts. Following infection, the virus alters the proteome of the infected cell and triggers anti-viral cellular immune responses. The infected cell’s altered proteome is reflected at the cell surface by the HLA (Human Leukocyte Antigen) class I molecule. Class I HLA sample and display endogenously loaded peptides at the surface of all nucleated cells so that CTL can distinguish infected from uninfected cells. To identify class I ligands that mark infected cells, we collect soluble HLA B*0702 and A*0201 molecules from influenza infected and uninfected cells. Peptide ligands and their class I carriers are size separated, uninfected and infected peptide pools are fractionated by RP-HPLC, and peptides are comparatively mapped via mass spectrometry. Thus far, we have identified B*0702 peptides derived from the Influenza A/PR/8 hemagglutinin and nucleoprotein molecules and multiple B*0702 and A*0201 host-derived peptides that are either uniquely expressed or up-regulated on the surface of influenza infected cells. The identification of viral peptides unique to the class I of influenza infected cells indicates a route for eliciting CTL via vaccination whilst changes in class I HLA presented self peptide epitopes indicate "danger" signals that demark the infected cell.
