Discovery and Characterization of a Novel Antiviral CD8 T cell Response Open Access

Swanson II, Phillip Alan (2009)

Permanent URL: https://etd.library.emory.edu/concern/etds/pz50gw19n?locale=en
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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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