RAT RT6.2 AND MOUSE RT6 LOCUS-1 ARE NAD(- ARGININE ADP RIBOSYLTRANSFERASES WITH AUTO-ADP RIBOSYLATION ACTIVITY() )

RT6 is a glycosylphosphatidylinositol-linked protein found on the surf ace of mature rat T lymphocytes, Cells that express RT6 have an immuno regulatory function and modulate the expression of autoimmune diabetes mellitus in the BioBreeding rat, A homologue of the rat RT6 gene, des ignated Rt6, has been identified in the mouse, but expression of mouse Rt6 protein has not been documented. Rat RT6 is known to be a nicotin amide adenine dinucleotide (NAD(+)) glycohydrolase. We now report that rat RT6.2 and recombinant mouse Rt6 locus 1 proteins possess auto-ADP ribosylation activity. in addition, mouse Rt6 but not rat RT6, cataly zes the ADP ribosylation of exogenous accepters such as histones. The ADP-ribosyl-protein bonds in auto-ADP-ribosylated rat RT6.2, auto-ADP- ribosylated mouse Rt6, and ADP-ribosylhistone synthesized by Rt6 were stable to HgCl2 and HCl, but labile to NH2OH, consistent with ADP ribo sylarginine linkages, To determine if these enzymatic activities could affect the function of rat T cells, the effect of substrate availabil ity on lymphocyte proliferation was examined, An inverse correlation w as observed between NAD(+) concentration in the medium and the ability of rat T cells to respond to anti-CD3, Con A, and PMA plus ionomycin. The data suggest that lymphocyte surface ADP ribosyltransferases coul d be involved in signaling and immunoregulatory processes.