Opportunities and challenges in development of phosphoantigens as Vγ9Vδ2 T cell agonists.
In contrast to T cells that express the more prevalent αβ T cell receptor and respond to peptide antigens, T cells that express the Vγ9Vδ2 T cell receptor detect and respond to non-peptide phosphorous-containing small molecules known as phosphoantigens. Because γδ T cells are early responders to infections and malignancies, it has been suggested that stimulation of their activity with small molecule phosphoantigen drugs may hold promise for therapeutic interventions. Recent studies have greatly advanced our knowledge of phosphoantigens as well as their cellular receptors. At the same time, clinical trials of phosphoantigens have suggested that development of these Vγ9Vδ2 T cell agonists has met unexpected challenges. In this commentary, we summarize the biology that underlies phosphoantigen activity and discuss the structural features of synthetic phosphoantigens that affect both their ability to stimulate Vγ9Vδ2 T cells and their potential as therapeutic agents.
['Wiemer|David F|DF|', 'Wiemer|Andrew J|AJ|']
D000818:Animals D000938:Antigen-Presenting Cells D000941:Antigens D003141:Communicable Diseases D006801:Humans D009369:Neoplasms D010710:Phosphates D010750:Phosphoproteins D016692:Receptors, Antigen, T-Cell, gamma-delta D016176:T-Lymphocyte Subsets
Phosphoantigen Bisphosphonate Gamma delta T cell Immunotherapy Isoprenoid Statin