TY - JOUR
T1 - Heteromeric interactions regulate butyrophilin (BTN) and BTN-like molecules governing γδ T cell biology
AU - Vantourout, Pierre
AU - Laing, Adam
AU - Woodward, Martin J.
AU - Zlatareva, Iva
AU - Apolonia, Luis
AU - Jones, Andrew W.
AU - Snijders, Ambrosius P.
AU - Malim, Michael H.
AU - Hayday, Adrian C.
PY - 2018/1/30
Y1 - 2018/1/30
N2 - The long-held view that gamma delta (γδ) T cells in mice and humans are fundamentally dissimilar, as are γδ cells in blood and peripheral tissues, has been challenged by emerging evidence of the cells’ regulation by butyrophilin (BTN) and butyrophilin-like (BTNL) molecules. Thus, murine Btnl1 and the related gene, Skint1, mediate T cell receptor (TCR)-dependent selection of murine intraepithelial γδ T cell repertoires in gut and skin, respectively; BTNL3 and BTNL8 are TCR-dependent regulators of human gut γδ cells; and BTN3A1 is essential for TCR-dependent activation of human peripheral blood Vγ9Vδ2+ T cells. However, some observations concerning BTN/ Btnl molecules continue to question the extent of mechanistic conservation. In particular, murine and human gut γδ cell regulation depends on pairings of Btnl1 and Btnl6 and BTNL3 and BTNL8, respectively, whereas blood γδ cells are reported to be regulated by BTN3A1 independent of other BTNs. Addressing this paradox, we show that BTN3A2 regulates the subcellular localization of BTN3A1, including functionally important associations with the endoplasmic reticulum (ER), and is specifically required for optimal BTN3A1-mediated activation of Vγ9Vδ2+ T cells. Evidence that BTNL3/BTNL8 and Btnl1/Btnl6 likewise associate with the ER reinforces the prospect of broadly conserved mechanisms underpinning the selection and activation of γδ cells in mice and humans, and in blood and extralymphoid sites.
AB - The long-held view that gamma delta (γδ) T cells in mice and humans are fundamentally dissimilar, as are γδ cells in blood and peripheral tissues, has been challenged by emerging evidence of the cells’ regulation by butyrophilin (BTN) and butyrophilin-like (BTNL) molecules. Thus, murine Btnl1 and the related gene, Skint1, mediate T cell receptor (TCR)-dependent selection of murine intraepithelial γδ T cell repertoires in gut and skin, respectively; BTNL3 and BTNL8 are TCR-dependent regulators of human gut γδ cells; and BTN3A1 is essential for TCR-dependent activation of human peripheral blood Vγ9Vδ2+ T cells. However, some observations concerning BTN/ Btnl molecules continue to question the extent of mechanistic conservation. In particular, murine and human gut γδ cell regulation depends on pairings of Btnl1 and Btnl6 and BTNL3 and BTNL8, respectively, whereas blood γδ cells are reported to be regulated by BTN3A1 independent of other BTNs. Addressing this paradox, we show that BTN3A2 regulates the subcellular localization of BTN3A1, including functionally important associations with the endoplasmic reticulum (ER), and is specifically required for optimal BTN3A1-mediated activation of Vγ9Vδ2+ T cells. Evidence that BTNL3/BTNL8 and Btnl1/Btnl6 likewise associate with the ER reinforces the prospect of broadly conserved mechanisms underpinning the selection and activation of γδ cells in mice and humans, and in blood and extralymphoid sites.
KW - Butyrophilins
KW - Endoplasmic reticulum
KW - Evolutionary conservation
KW - Gamma delta T cells
KW - Zoledronate
UR - http://www.scopus.com/inward/record.url?scp=85041198144&partnerID=8YFLogxK
U2 - 10.1073/pnas.1701237115
DO - 10.1073/pnas.1701237115
M3 - Article
AN - SCOPUS:85041198144
SN - 0027-8424
VL - 115
SP - 1039
EP - 1044
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 5
ER -