Discovery and Characterization of a Novel Antiviral CD8 T cellResponse 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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