The Univeristy of Melbourne The Royal Melbourne Hopspital

A joint venture between The University of Melbourne and The Royal Melbourne Hospital

EDUCATION

Research Projects

Project: Recognition of phosphoantigens by gamma-delta (γδ) T cells

Godfrey Group

Gamma-delta (γδ) T cells are a critically important component of the immune system. They are often enriched in non-lymphoid tissues and respond rapidly to infection by producing inflammatory cytokines, proliferating and acquiring cytotoxicity potential. Unlike alpha-beta (αβ) T cells, which primarily respond to antigenic peptides in the context of MHC, most γδ T cells in humans react to small phosphorylated non-peptide molecules called ‘phosphoantigens’. However, the molecular mechanism underpinning this recognition is a mystery. In the 25 years since the discovery of phosphoantigens, researchers have confirmed that some form of antigen-presenting molecule other than MHC is important, however, the identity of this ligand was a mystery. We have recently discovered that a surface protein called ‘butyrophilin 2A1’ is critical and enables γδ T cells to respond to phosphoantigen (ref #1). We are offering a project to further explore this novel form of antigen presentation, including an examination of how phosphoantigen-binding triggers γδ T cells to become activated, and whether other ligands are involved. Answers to these fundamental questions will hopefully lead to the development of new treatments for cancer, as well as infectious disease.

Image: Human gamma-delta (γδ) T cells become activated in response to microbial and cancer-derived phosphoantigens, and we have discovered that a cell-surface protein called “butyrophilin 2A1” is essential, and that it functions in cooperation with another related molecule called “butyrophilin 3A1”. Together, these molecules bind to the T cell receptor expressed on γδ T cells and initiate an immune response.

Ref #1. Marc Rigau et al. Butyrophilin 2A1 is essential for phosphoantigen reactivity by γδ T cells. Science. 2020 Feb 7;367(6478):eaay5516.

Contact project supervisor for further
information and application enquiries

Project Supervisor

Dr Adam Uldrich

Project Co-supervisor

Professor Dale Godfrey

Project availability
PhD/MPhil
Master of Biomedical Science
Honours

Godfrey Group

godfrey@unimelb.edu.au

1 vacancies

Themes
Immunology
Cross Cutting Disciplines

The Godfrey Lab has a strong track record in the field of unconventional T cells with a focus on CD1 restricted cells (NKT cells); MR1-restricted T cells (MAIT cells) and gamma delta T cells (1). These cells play a key role in many different diseases. More recently, we are also examining the role that these and other immune cells play in COVID-19 disease. The ultimate aim of this research is to understand the mechanisms with which these unconventional T cell populations specifically contribute to the immune response and how they can be harnessed for immunotherapy.


Godfrey Group Current Projects