BTNL8, a butyrophilin-like molecule that costimulates the primary immune response

•The manuscript describes a new function for BTNL8 (butyrophilin-like 8 molecule).•Our data indicate that BTNL8 costimulates Ag specific immune response.•Regulation of BTNL8 function can be used for the immunomodulation of T lymphocytes.

The role of the B7 family molecules in the regulation of the immune response is well documented. A large body of experimental evidence indicates that costimulatory molecules such as B7-1, B7-2, B7-DC, B7-H1, B7-H2, B7-H3 and B7-H4 are critical for initiation, maintenance and down-regulation of the immune response. However the immunological function of butyrophilin (BTN)-like molecules, which are a part of the expanded B7 family, is not known. Here, we demonstrate that the extracellular portion of human BTNL8 can augment Ag-induced activation of T lymphocytes. BTNL8 has two alternatively spliced forms: B7-like and BTN-like. Both isoforms of BTNL8 were expressed concurrently in various human tissues. A putative BTNL8 receptor was detected only on resting T lymphocytes. Administration of BTNL8Ig fusion protein into mice promoted production of Ag-specific IgG during the primary, but not the secondary immune responses. BTNL8 may therefore play an essential role in priming of naïve T lymphocytes.