Semaphorin receptors in the immunological synapse: regulation and measles virus-driven modulation [Elektronische Ressource] = Semaphorinrezeptoren in der immunologischen Synapse: Regulierung und masernvirusgesteuerte Modulation / submitted by Hieu Tran-Van

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• Publié par: julius-maximilians-universitat_wurzburg
• Publié le: 01 janvier 2010
• Nombre de lectures: 25
• Langue: English
• Poids de l'ouvrage: 4 Mo

Extrait

Semaphorin receptors in the immunological
synapse: regulation and measles virus-driven
modulation
Semaphorinrezeptoren in der immunologischen
Synapse: Regulierung und
masernvirusgesteuerte Modulation
Doctoral thesis for a doctoral degree
at the Graduate School of Life Sciences,
Julius-Maximilians-Universität Würzburg
Section: Infection and Immunity
Submitted by
HIEU TRAN-VAN
from
Nha Trang, Viet Nam
Würzburg 2010Submitted on:....................................................................................................................
Members of the Promotionskomitee:
Chairperson: Prof. Dr. Thomas Dandekar
Primary Supervisor: Prof. Dr. Sibylle Schneider-Schaulies
Supervisor (Second): Prof. Dr. Peter Friedl
Supervisor (Third): Prof. Dr. Marie Christine Dabauvalle
Date of public defence:....................................................................................................
Date of Receipt of Certificates:.......................................................................................For the Hs,
H2 and CCDECLARATION | i
I hereby declare that my thesis entitled “Semaphorin receptors in the immunological
synapse: regulation and measles virus-driven modulation” is the result of my own work. I
did not receive any help or support from commercial consultants. All sources and/or
materials applied are listed and specified in the thesis.
Furthermore; I verify that this thesis has not yet been submitted as part of another
examination process neither in identical nor in similar form.
ndWürzburg, ..........September 2.................... , 2010......................................................................Hieu Tran....................-Van....................
Date Signature ACKNOWLEDGEMENT | ii
I would like to acknowledge my supervisor committee for their tutoring and mentoring. My
grateful thank goes to Prof. Sibylle Schneider-Schaulies, my first supervisor as well as my
boss, for her education and expert guidance on my project that help me to be more
“mature” in term of scientific abilities. For funding support and program mentoring, I
would like to express my appreciation to the Graduate school of Life Sciences, Graduate
college of Immunomodulation, which is now renamed Graduate program of
Immunomodulation, and their staff as well.
I am indebted to my lab mates, ‘Spiderman’ Ibo, ‘mafia-in’ Eve, ‘Snow White’ Elita, ‘süße’
Susi, ‘nachbar’ Andi, Meena, Alice, for their nice support at my very first days in Germany. I
am also grateful to Babara, Bea, ‘Sonnenschein’ Charlene and Caro for their expert technical
assistance. Others I would like to thank are Katrin and the neighbor group for their willing
to swap materials and eagents, Dr. Avota for her infinite patience to explain and give
suggestions.
I would like to express my gratitude to Dr. Harry Harms and Dr. Nora Müller for their
invaluable work on imaging documentation, Dr. Rik de Swart, Dr. Martin Ludlow and Rory
in Erasmus MC, Rotterdam, The Netherlands for their help in monkey tissue samples, Dr.
Michael Sixt in MPI of Biochemistry, Munich for an interesting collaboration, Dr. Luca
Tamagnone in IRCC, Turin for his generosity in providing me with human plexA1
constructs using in this project and last but not least, Prof. Jürgen Schneider-Schaulies and
Prof. Georg Kohne for their useful comments and creative discussion.
For non-scientific life, I wish to thank the ladies in Guest House of University of Würzburg
for showing me how wonderful Germans and Germany are by their willing to organize
weekly excursions and culture events.
Thank my friend Duy Phan for his not only critical help in linguistics but also precious
advice in scientific activities. I wish to acknowledge any anonymous whose useful projects
and information do not include here due to limited space and many thanks to blood donors
who made this project possible.
My final but most honest thanks go to Huy Phan for his resolution to computer related
issues as well as advice in image and software difficulties and my family for their
unconditional love and support that make my life enjoyable.ABBREVIATION | iii
Akt serine/threonine-specific protein kinase
BSA bovine serum albumin
CDK cyclin-dependent kinase
CFSE carboxyfluorescein succinimidyl ester
CIITA class II transactivator
CPE cythopathic effect
CQ chloroquine
CRMP collapsin response mediator protein
CUB complement binding
DC dendritic cell
DRM detergent-resistant membrane microdomain
ER endoplasmic reticulum
ERM ezrin/radixin/moesin
FASC fluorescence activated cell sorting
FCS fetal calf serum
FIP fusion inhibitory peptide
GAP GTPase-activating protein
GEF guanyl nucleotide exchange factors
ICAM inter-cellular adhesion molecule
IF Immunofluorescence
Ig immunoglobulin
IL interleukin
IP immunoprecipitation
IS immunological synapse
LARG leukemia-associated Rho GEF
LFA leukocyte function associated antigen
LIMK LIM domain kinase
LPS lipopolysaccharide
MAM merphin A5
MDDC monocyte-derived dendritic cells
MHC major histocompatibility complexABBREVIATION | iv
MICAL molecule interacting with CasL
MLR mixed lymphocyte reaction
MTOC microtubulin organizing center
MV measles virus
NP neuropilin
PAK p21- activated kinase
PAO phenylarsine oxide
PBL peripheral blood leukocyte
PDZ PSD-95/Dlg/ZO-1
PFA paraformaldehyde
PI3K phosphatidylinositol-3 kinase
PKC protein kinase C
plex plexin
PLL poly-L-lysine
R18 octadecyl rhodamine B chloride
RNP ribonucleoprotein
ROCK Rho-associated coiled-coil containing kinase
SCR short consensus repeats
SEMA semaphorin
SHIP Src homology domain 2 containing inositol-5-phosphatase
SLAM signaling lymphocytic activation molecule
SMAC supramolecular activation cluster
TCR T cell receptor
Th T helper
TIM T-cell immunoglobulin domain and mucin domain
TLR Toll-like receptor
TRAIL TNF-related apoptosis-inducing ligand
UV ultraviolet
VSV vesicular stomatitis virus
WASp Wiskott-Aldrich Syndrome protein
WAVE WASP family Verprolin-homologous protein
WB Western blot
ZAP ζ-chain associated protein CONTENTS | v
Declaration ............................................................................................................................................ i
Acknowledgement ............................................................................................................................... ii
Abbreviation........................................................................................................................................iii
Contents...............................................................................................................................................vi
1. Introduction................................................................................................................................ 2
1.1. Measles...................................................................................................................................... 2
1.1.1. MV morphology and genome structure....................................................................... 3
1.1.1.1. Virus morphology ................................................................................................ 3
1.1.1.2. Genome structure ................................................................................................ 3
1.1.2. MV receptor usage.......................................................................................................... 7
1.1.2.1. CD46...................................................................................................................... 7
1.1.2.2. CD150.................................................................................................................... 8
1.1.2.3. Unidentified cellular receptor(s)......................................................................... 9
1.1.3. MV-induced immunosuppression ................................................................................ 9
1.1.3.1. Lymphopenia ...................................................................................................... 10
1.1.3.2. MV-driven modulation of DC viability and function ................................... 10
1.1.3.3. MV-infected DC-induced T cell suppression................................................. 11
1.1.3.4. Viral proteins modulating or silencing T cells................................................ 11
1.1.3.5. Surface receptor(s) involved in silencing of T cells....................................... 13
1.1.3.6. Signaling pathways targeted by MV................................................................. 13
1.2. DC-T cell interaction............................................................................................................ 14
1.2.1. Immunological synapse ................................................................................................ 14
1.2.2. Termination of immune response .............................................................................. 17
1.3. Semaphorins and their role in cell morphology and immune modulation ................... 17
1.3.1. SEMA receptors..................................................................................