Discovery and Characterization of a Novel Antiviral CD8 T cell Response Open Access
Swanson II, Phillip Alan (2009)
Published
Abstract
Abstract
Discovery and Characterization of a Novel Antiviral CD8 T cell
Response
By Phillip Alan Swanson II
Immunity to viral infection is primarily provided by CD8 T cells
that recognize
pathogen-derived peptides presented by MHC class Ia molecules,
however little attention
has been devoted to whether MHC class Ib molecules also have a role
in the antiviral
CD8 T cell response. Using the persistent mouse pathogen polyoma
virus (PyV) model,
we identified an MHC class Ib-restricted antiviral CD8 T cell
response in infected MHC
class Ia-deficient (Kb-/-Db-/-) mice. PyV-specific CD8 T cells in
infected Kb-/-Db-/- mice
recognize a viral peptide derived from the VP2 capsid protein
(VP2.139) presented by the
class Ib molecule Q9. The Q9/VP2.139-specific CD8 T cells are both
protective and
long-lived in PyV-infected Kb-/-Db-/- mice. Importantly, these
cells are also detected in
both acute and persistent PyV-infected wild type mice. Although the
Q9-restricted anti-
PyV CD8 T cell response represents the first identification and
characterization of an
endogenous class Ib-restricted antiviral CD8 T cell response, the
ubiquitous tissue
expression and peptide-binding capabilities of several different
class Ib molecules
indicate that they could be involved in a diverse array of
antiviral responses. From a
therapeutic standpoint, CD8 T cell vaccines targeting class
Ia-restricted viral epitopes
only provide partial protection across a population due to the high
polymorphism
associated with these molecules. Vaccines using nonpolymorphic
class Ib-restricted CD8
T cell epitopes could provide broad protection across haplotype
barriers.
Table of Contents
Table of Contents
Abstract
Table of Contents
List of Figures/Tables
Chapter 1: Introduction
CD8 T cell antiviral immunity
........................................................................................
1
PyV as a Model System for Studying Peresistent Viral
Infection..................................... 7
MHC class Ib molecules in immunity
...........................................................................
13
Chapter 2: An MHC class Ib-restricted CD8 T cell response
confers
antiviral immunity
Abstract
........................................................................................................................
21
Introduction
..................................................................................................................
22
Results
..........................................................................................................................
25
Discussion
....................................................................................................................
33
Materials and
Methods..................................................................................................
38
Chapter 3: Shift in Antigen Dependence by an Antiviral MHC Class
Ib-
restricted CD8 T Cell Response During Persistent Viral
Infection
Abstract
........................................................................................................................
52
Introduction
..................................................................................................................
53
Materials and
Methods..................................................................................................
55
Results and
Discussion..................................................................................................
57
Chapter 4: Discussion
...........................................................................................
68
References
................................................................................................................
80
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