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F1000Res. 2017 Jun 5;6. pii: F1000 Faculty Rev-782. doi: 10.12688/f1000research.11057.1. eCollection 2017.

Immunosurveillance by human γδ T lymphocytes: the emerging role of butyrophilins.

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Institute of Immunology, University of Kiel and University Hospital Schleswig-Holstein Campus Kiel, Arnold-Heller-Str. 3, Building 17, D-24105 Kiel, Germany.


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.


Immunosurveillance; T-cell; butyrophilins; immunotherapeutic; lymphocytes

Conflict of interest statement

Competing interests: The authors declare that they have no competing interests.No competing interests were disclosed.No competing interests were disclosed.

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