THE LYMPHOCYTE SURFACE-ANTIGEN CD38 ACTS AS A NICOTINAMIDE ADENINE-DINUCLEOTIDE GLYCOHYDROLASE IN HUMAN T-LYMPHOCYTES

The extracellular domain of the lymphocyte surface antigen CD38 has be en recently shown to share a high sequence homology with a nicotinamid e adenine dinucleotide (NAD+)-specific hydrolyzing enzyme cloned from the ovotestis of the gastropod Aplysia (E. States, D. J., Walseth, T. E, Lee, H. C., Trends Biochem. Sci. 1992. 17: 495). In agreement with this finding, we present here evidence that CD38-overexpressing T cell s, such as human thymocytes and cells from the human HPB-ALL T cell li ne, exhibit a NAD+-hydrolyzing enzymatic activity present on the outer surface of the cell membrane. In contrast, T lymphocytes with relativ ely low levels of CD38 marker, such as the human Jurkat cell line, dis play a lower activity. This suggests a relationship between ecto-NADglycohydrolase activity and CD38 expression, as confirmed here when co mparing wild-type Jurkat cells and a Jurkat cell variant overexpressin g the CD38 molecule. Moreover, CD38 immunoprecipitates from thymocytes behave as an authentic NAD+ glycohydrolase enzyme: it transforms NAD stoichiometrically into nicotinamide plus adenosine 5'-diphosphoribos e. Altogether these results strongly support the assumption that CD38 is actually a lymphocyte-specific NAD+-hydrolyzing enzyme, a finding t hat give new prospects to understand the in vivo function of this cell membrane protein.