Epigenetic Regulation of T Cell Function - Lecture Notes

Introduction

  • Speaker: Steve Turner, Head of Microbiology at Monash University.

  • Focus of research: Molecular mechanisms promoting optimal immunity against virus infection in tumors.

  • Key areas of study:
      - Dynamic changes in genome structure.
      - Modifications within the genome influencing gene expression.
      - Impact on T cell immunity establishment.

  • Lecture Title: Epigenetic Regulation of T Cell Function.

Contact Information

  • Email Address: (given in presentation).

  • Twitter Account: (handle provided in presentation).

  • Areas of Interest: Science-related topics, T cell biology, immunology.

Learning Objectives

  • Understand the role of post-translational modifications (PTMs) of histone proteins in gene transcription regulation.

  • Explore how these mechanisms influence T cell activation outcomes and establishment of immunological memory.

Cardinal Features of Adaptive Immunity

  • Specificity: Refers to antigen receptors found on B cells and T cells. Each receptor has unique specificity due to:   - Gene recombination.   - Inefficient gene splicing leading to a diverse receptor array.

  • Diversity: The immune system's ability to cover a wide range of potential pathogens.

  • Activation and Differentiation:   - Immune cells initially lack function, but upon activation, they undergo differentiation to acquire lineage-specific functions.   - B cells: Produce antibodies.   - CD4 T helper cells: Produce cytokines.   - Killer T cells: Produce cytolytic molecules.

  • Immunological Memory:   - Activated cells do not revert to an initial inactive state.   - Retain functions acquired during the primary immune response for quicker, more robust responses during secondary challenges.   - Basis for vaccine efficacy.

Functional Mechanisms of T Cells

  • Focusing on T cells, particularly CD4 T helper cell subsets.

  • Naive CD4 T cells: Begin without function; can be activated by signals to develop specific functions.   - Activation by Interleukin-12 (IL-12) leads to Th1 polarization and production of interferon-gamma (IFN-γ).   - Activation by Interleukin-4 (IL-4) leads to Th2 polarization and production of IL-4.

Subtypes of CD4 T Helper Cells

  • Multiple subtypes of CD4 T helper cells influenced by activation signals:   - Th1: Produces IFN-γ, key transcription factor is TBX21.(encoded by TBX21 gene).   - Th2: Produces IL-4, key transcription factor is GATA3.   - Th17: Produces IL-17, key transcription factor is RORγt.   - Regulatory T cells (Tregs): Critical in regulating immune function, key transcription factor is FOXP3.

  • Importance of transcription factors: Essential in determining functional outcomes and differentiation of T cell subsets.

Cytotoxic T Cells (CD8 T Cells)

  • CD8 T cells are mainly known for their cytolytic function.

  • Regulated by:   - Transcription factors like T-bet (associated with Th1) and Eomesodermin (Eomes).

  • Key point on transcription factors:   - The ability of transcription factors to bind to specific genomic areas is essential for the functional capabilities of T cells.

Chromatin Biology Introduction

  • Focus on the regulation of chromatin structure and its influence on transcription factor functioning.

  • Discussions will encompass the importance of the chromatin environment in T cell differentiation and function.

Summary and Next Steps

  • Next session will provide an introduction to chromatin biology and its relevance to T cells and immune functions.

  • Speaker expresses gratitude for participation and looks forward to the next lecture.