BTN3A1 antibodies and phosphoantigens: TCRVg9Vd2 "see" the difference
Human blood gd T lymphocytes express TCRVg9Vd2 and respond to nonpeptide phosphoantigens (PAgs) by a mysterious mechanism involving the BTN3A1 (CD277) molecule BTN3A1 is a butyrophilin like protein related to CD80, PD L1, and MHC, and is either a presenting or a co stimulatory molecule for PAgs. Although the precise roles and molecular interactions with the TCRVg9Vd2 are currently not determined, it is commonly thought that all TCRVg9Vd2 lymphocytes 'see' PAg and BTN3A1 together, presumably in a single molecular recognition event. But whether this recognition event could be reproduced in a simplified model was not addressed in previous studies. In this issue, Starick et al. (Eur. J. Immunol. 2017. 47: 982 992) compared the response of three TCRVg9Vd2 pairs of murine and human cell transfectants to PAg and anti BTN3A1 antibodies using IL 2 release as a readout. The authors found that although the two murine transfectants responded similarly to either stimuli, one murine TCRVg9Vd2 transfectant reacted to PAgs but not to anti BTN3A1 (mAb 20.1) Human transductants behave in a similar fashion, demonstrating that TCRVg9Vd2 lymphocytes differentiate PAg and BTN3A1 signals, while species of the transductants unmask this differential sensitivity. Indeed, understanding the puzzling mode of antigen recognition by gd T lymphocytes will be essential for developing gd T cell based immunotherapies, and the authors of this study now demonstrate that TCRVg9Vd2 lymphocytes are able to differentiate the PAg and BTN3A1 stimuli.
European journal of immunology