Unchanged signaling capacity of mutant CD26/dipeptidylpeptidase IV molecules devoid of enzymatic activity.

CD26 is a proteolytic enzyme (dipeptidylpeptidase IV) that defines an alternative activation signal for human T lymphocytes. Crosslinking of CD26 via monoclonal antibodies triggers proliferation and cytotoxicity in CD26-positive T cells or provides costimulatory signals for these cells. Because there is some debate about whether the enzymatic activity plays a role in activation via CD26 we have here generated a mutant CD26 molecule devoid of enzymatic activity. After transfection into T cell receptor-positive recipient T cells, such mutant molecules were tested for their signaling capacity compared to that in the wildtype molecules. The response of transfected clones to direct stimulation with anti-CD26 antibodies and to costimulation via CD26 was variable and not solely dependent on the amount of CD26 and T cell receptor expressed on the T cells. Several mutant transfectants were more easily triggered via CD26 than cells transfected with the wildtype molecule. These data demonstrate that the enzymatic activity of CD26 is not required for its T cell activating or costimulating properties.