In vitro processing and presentation of a lipidated cytotoxic T-cell epitope derived from measles virus fusion protein

Lipopeptidic formulations have been described as efficient activators of cytotoxic T lymphocytes (CTL). To better understand the pathway via which lipopeptides reach the MHC class I molecules we studied the intracellular processing and presentation of a measles virus-derived CTL epitope, to which a...

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Bibliographic Details
Published in:Vaccine 2001-10, Vol.20 (1), p.249-261
Main Authors: Stittelaar, Koert J, Hoogerhout, Peter, Ovaa, Wim, van Binnendijk, Robert R.S, Poelen, Martien C.M, Roholl, Paul, van Els, Cécile A.C.M, Osterhaus, Albert D.M.E, Wiertz, Emmanuel J.H.J
Format: Article
Language:English
Subjects:
Antigen Presentation
Antigen processing
ATP Binding Cassette Transporter, Subfamily B, Member 2
ATP Binding Cassette Transporter, Subfamily B, Member 3
ATP-Binding Cassette Transporters - genetics
ATP-Binding Cassette Transporters - metabolism
Biological and medical sciences
Brefeldin A - pharmacology
Cell Line, Transformed - immunology
Cells, Cultured - immunology
Cysteine Endopeptidases - metabolism
Endoplasmic Reticulum - metabolism
Epidemiology. Vaccinations
Epitopes - chemistry
Epitopes - immunology
Fundamental and applied biological sciences. Psychology
General aspects
Golgi Apparatus - metabolism
HLA Antigens - immunology
Humans
Infectious diseases
Lipopeptides
Lipoproteins - immunology
Lipoproteins - metabolism
Lymphocyte Activation
Measles virus
Measles virus - immunology
Medical sciences
Micelles
Microbiology
Microscopy, Confocal
Microscopy, Fluorescence
Multienzyme Complexes - metabolism
Palmitic Acid - chemistry
Peptide Fragments - chemistry
Peptide Fragments - immunology
Proteasome Endopeptidase Complex
Protein Transport - drug effects
T-Lymphocytes, Cytotoxic - immunology
Tumor Cells, Cultured - drug effects
Tumor Cells, Cultured - immunology
Tumor Necrosis Factor-alpha - pharmacology
U937 Cells - metabolism
Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies
Viral Fusion Proteins - chemistry
Viral Fusion Proteins - immunology
Virology
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Summary:Lipopeptidic formulations have been described as efficient activators of cytotoxic T lymphocytes (CTL). To better understand the pathway via which lipopeptides reach the MHC class I molecules we studied the intracellular processing and presentation of a measles virus-derived CTL epitope, to which a palmitoyl moiety was added synthetically. The palmitoyl group was conjugated to the N-terminus either directly or via a spacer sequence. The use of single or double fluorescent-labeled lipopeptides allowed the visualization of intracellular processing of these antigens using confocal microscopy. Our data indicate that the spacer composition influences internalization of the conjugate into the cell, proteasomal degradation, translocation into the ER by the transporter associated with antigen processing (TAP), and the intracellular trafficking of lipopeptides.
ISSN:0264-410X
1873-2518
DOI:10.1016/S0264-410X(01)00265-1