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-gamma or TNF-alpha. 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.
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