We thank Dr. Herrmann for the thoughtful critiques and comments on our recent publication (1). We agree with Dr. Herrmann that both clone 20.1 and 103.2 monoclonal antibodies bind all human BTN3A isoforms, including BTN3A1, BTN3A2, and BTN3A3. Thus, both clones are not BTN3A1-specific antibodies. In our publication, Vγ9Vδ2 T cell activation in both total PBMCs and monocytes+Vγ9Vδ2 T cells culture system was stimulated with pAgs throughout the study (2). It has been shown that pAg-induced Vγ9Vδ2 T cell activation is dependent on BTN3A1, not BTN3A2 and BTN3A3 in the BTN3A family (3–5). Based on the data that clone 103.2 (Creative Biolabs, Catalog number PABL-415) can inhibit HMBPP-induced Vγ9Vδ2 T cell activation, we conclude that the blocking effect of clone 103.2 is medicated through BTN3A1 in the context of pAg-induced Vγ9Vδ2 T cell activation.
Secondly, figure 3B in our study has shown that Vγ9Vδ2 T cells can present pAgs to themselves, leading to self-activation (2). In addition, the expression of BTN3A on the surface of Vγ9Vδ2 T cells is elevated in psoriasis (2). These findings suggest that hyperactivation of Vγ9Vδ2 T cells in psoriasis might be due to their self-interaction, in addition to the interaction with CD14+ monocytes. Given the low frequency of Vγ9Vδ2 T cells in the blood, the possibility of self-activation in vivo appears to be low. We have included this point in the discussion section (2).
In addition, we titrated clone 103.2 antibody to obtain the optimal dose for its blocking effect on pAg-induced Vγ9Vδ2 T cell activation (2). The results have shown that clone 103.2 inhibits pAg-induced Vγ9Vδ2 T cell activation in a dose-dependent manner. These data indicate that the BTN3A1 expression level positively correlates with the extent of pAg-induced Vγ9Vδ2 T cell activation, which further supports the notion that overactive Vγ9Vδ2 T cells in psoriasis are due to the increased expression of BTN3A1 on CD14+ cells.
We agree that BTN3A1 has a complex role given that it can regulate multiple immune cell functions. Thus, it is necessary to evaluate the therapeutic potential of BTN3A1 in vivo in different disease contexts by using genetic-engineered mouse models or blocking antibodies. Our recent study only determined the role of BTN3A1 in Vγ9Vδ2 T cell activation in the in vitro setting (2). Further investigations are needed to fully characterize the function of BTN3A1 in the future.
Acknowledgments
Author contributions
J. Zhou, J. Zhang, Z.Z., and L.S. wrote the paper.
Competing interests
The authors declare no competing interest.
References
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