Processing of filamentous bacteriophage virions in antigen-presenting cells targets both HLA class I and class II peptide loading compartments

Gaubin, Muriel, Fanutti, Cristina, Mishal, Zohar, Durrbach, Antoine, De Berardinis, Piergiuseppe, Sartorius, Rossella, Del Pozzo, Giovanna, Guardiola, John, Perham, Richard N. and Piatier-Tonneau, Dominique (2003) Processing of filamentous bacteriophage virions in antigen-presenting cells targets both HLA class I and class II peptide loading compartments. DNA and Cell Biology, 22 (1). pp. 11-18. ISSN 1557-7430

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Abstract

Virions of filamentous bacteriophage fd are capable of displaying multiple copies of peptide epitopes and generating powerful immune responses to them. To investigate the antigen processing mechanisms in human B cell lines used as antigen presenting cells, the major coat protein (pVIII) in intact virions was fluorescently labeled, and its localization in various intracellular compartments was followed using confocal microscopy. We show that the virions were taken up and processed to yield peptides that reach both the major histocompatibility complex (MHC) class II compartment and the endoplasmic reticulum. Moreover, when exposed to bacteriophages displaying a cytotoxic T lymphocyte (CTL) epitope from the reverse transcriptase of human immunodeficiency virus type-1 (HIV-1), B cells were lysed by specific cytotoxic lymphocytes. This confirms that filamentous bacteriophage virions are capable of being taken up and processed efficiently by MHC class I and class II pathways, even in nonprofessional antigen presenting cells. These remarkable features explain, at least in part, the unexpected ability of virions displaying foreign T-cell epitopes to prime strong T-helper-dependent CTL responses. These findings have important implications for the development of peptide-based vaccines, using filamentous bacteriophage virions as scaffolds.

Item Type:	Article
Faculty \ School:	Faculty of Medicine and Health Sciences > Norwich Medical School
Depositing User:	EPrints Services
Date Deposited:	25 Nov 2010 11:09
Last Modified:	18 Mar 2024 17:30
URI:	https://ueaeprints.uea.ac.uk/id/eprint/12638
DOI:	10.1089/104454903321112451

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