New members of the B7 family have been recently described as regulators of T cell activation and function. Butyrophilin (BT) has also been related to the B7 family by sequence similarity analyses. We present a new subfamily called BT3, which belongs to the B7/BT family. The BT3 subfamily comprises three members (BT3.1, .2 and .3) that exhibit 95% identity and form a monophylogenetic group along with the BT‐related members. High expression levels of BT3 transcripts were detected in lymphoid tissues (mainly spleen, lymph node and PBL). Using anti‐BT3 mAb we could demonstrate BT3 expression on immune cells including T, B and NK cells, monocytes and dendritic cells as well as hematopoietic precursors and some tumor cell lines. As described earlier for PDL‐1 and ICOS‐L, BT3 molecules are expressed on endothelial cells and up‐regulated upon activation by IFN‐γ or TNF‐α. The BT3.1 counter‐receptor (BT3.1‐R) was analyzed by means of binding experiments using BT3.1‐Ig soluble protein. The BT3.1‐R is not CD28, CTLA‐4, ICOS, PD‐1 or BTLA and seems restricted to some T cell and hematopoietic cell lines. Altogether, these data describe new members of the B7/BT family that may play a role in regulation of the immune response.

See accompanying commentary http://dx.doi.org/10.1002/eji.200425388