THE STRUCTURE AND FUNCTION OF CD26 IN THE T-CELL IMMUNE-RESPONSE

CD26 is a widely distributed 110 kD cell-surface glycoprotein with kno wn dipeptidyl-peptidase IV (DPP-IV) activity in its extracellular doma in. This ecto-enzyme is capable of cleaving amino terminal dipeptides from polypeptides with either L-proline or L-alanine in the penultimat e position. On human T cells, CD26 expression appears late in thymic d ifferentiation and is preferentially restricted to the CD4(+) helper/m emory population, and CD26 can deliver a potent co-stimulatory T-cell activation signal. The cDNA sequence of CD26 predicts a type II membra ne protein with only 6 amino acids in its cytoplasmic region, suggesti ng that, in addition to DPP-IV enzyme activity, other signal-inducing molecules may be associated with CD26. Considerable evidence exists th at CD26 interacts, presumably in its extracellular domain, with both C D45, a protein tyrosine phosphatase, and adenosine deaminase (ADA), ea ch of which is capable of functioning in a signal transduction pathway In addition, CD26 is the receptor for ADA, and ADA on the cell surfac e is involved in an important immunoregulatory mechanism by which rele ased ADA binds to the cell-surface ADA. This multifunctional molecule may be involved in cell migration and the HIV-l-associated loss of CD4 (+) cells through the process of programmed cell death. Thus, CD26 app ears to play a key role in a number of aspects of lymphocyte function.