Immunosurveillance by human γδ T lymphocytes: the emerging role of butyrophilins [version 1; referees: 2 approved]

• Main Authors: Dieter Kabelitz, Marcus Lettau, Ottmar Janssen
• Format: Article
• Language: English
• Published: F1000 Research Ltd 2017-06-01
• Series: F1000Research
• Subjects: Antigen Processing & Recognition; Cell Growth & Division; Genetics of the Immune System; Immunity to Infections; Immunomodulation; Immunopharmacology & Hematologic Pharmacology; Innate Immunity; Leukocyte Activation; Leukocyte Development
• Online Access: https://f1000research.com/articles/6-782/v1

In contrast to conventional T lymphocytes, which carry an αβ T-cell receptor and recognize antigens as peptides presented by major histocompatibility complex class I or class II molecules, human γδ T cells recognize different metabolites such as non-peptidic pyrophosphate molecules that are secreted by microbes or overproduced by tumor cells. Hence, γδ T cells play a role in immunosurveillance of infection and cellular transformation. Until recently, it has been unknown how the γδ T-cell receptor senses such pyrophosphates in the absence of known antigen-presenting molecules. Recent studies from several groups have identified a unique role of butyrophilin (BTN) protein family members in this process, notably of BTN3A1. BTNs are a large family of transmembrane proteins with diverse functions in lipid secretion and innate and adaptive immunity. Here we discuss current models of how BTN molecules regulate γδ T-cell activation. We also address the implications of these recent findings on the design of novel immunotherapeutic strategies based on the activation of γδ T cells.