Mouse anti-Human BTN3A1 monoclonal antibody, clone CU4.2 [Biotin]

Studies of aryl phosphonate derivatives of a butyrophilin 3A1 ligand have resulted in identification of a potent stimulant of V gamma 9 V delta 2 T cells. This compound, a mixed ester bearing one pivaloyloxymethyl substituent and one 1-naphthyl ester displayed an EC50 of 0.79 nM as a stimulant of T cell proliferation, and a 9.0 nM EC50 in an assay designed to measure interferon gamma production. In both assays, this is the most potent butyrophilin ligand prodrug yet reported, and thus it should be a valuable tool for studies of T cell function. Furthermore, mixed aryl/acyloxyalkyl esters may represent a new class of phosphonate prodrugs with high efficacy.

V gamma 9V delta 2 T lymphocytes are the major human peripheral gamma delta T cell subset, with broad reactivity against stressed human cells, including tumor cells. V gamma 9V delta 2 T cells are specifically activated by small phosphorylated metabolites called phosphoantigens (PAg). Stress-induced changes in target cell PAg levels are specifically detected by butyrophilin (BTN) 3A1, using its intracellular B30.2 domain. This leads to the activation of V gamma 9V delta 2 T cells. In this study, we show that changes in the juxtamembrane domain of BTN3A1, but not its transmembrane domain, induce a markedly enhanced or reduced gd T cell reactivity. There is thus a specific requirement for BTN3A1' s juxtamembrane domain for correct gd T cell-related function. This work identified, as being of particular importance, a juxtamembrane domain region of BTN3A molecules identified as a possible dimerization interface and that is located close to the start of the B30.2 domain.