ITEMS

modern scholarly publishers in the finest tradition

Journals

	Search

Critical Reviews™ in Immunology

ISSN for PRINT: 1040-8401

Institutional price:	$831.00
Issues per year:	6

Best Paper Award Selection - Editorial Board Site

2007, Volume27

82 pages

Issue price - $153.00

Enzymatic and Extraenzymatic Role of Adenosine Deaminase 1 in T-Cell-Dendritic Cell Contacts and in Alterations of the Immune Function

Rafael Franco
Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Barcelona; and Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain

Rodrigo Pacheco
Millennium Nucleus on Immunology and Immunotherapy, Department of Molecular Genetics and Microbiology, Faculty of Biological Sciences, Pontificia Universidad Católica de Chile, Santiago de Chile, Chile

Josep Maria Gatell
Institut d'Investigacions Biomèdiques August Pi i Sunyer; and Service of Infectious Diseases and AIDS Unit, Hospital Clinic de Barcelona, Barcelona, Spain

Teresa Gallart
Institut d'Investigacions Biomèdiques August Pi i Sunyer; and Service of Immunology, Hospital Clinic de Barcelona, Barcelona, Spain

Carme Lluis
Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Barcelona; and Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain

ABSTRACT

Adenosine deaminase 1 (ADA1) is an enzyme of the purine metabolism whose congenital defect leads to severe combined immunodeficiency (SCID). Although classically considered a cytosolic enzyme, early evidence from work in brain synaptosomes suggested that the enzyme could be an ectoenzyme. In lymphoid cells, ectoenzymatic activity of ADA1 was also found. The obvious role of this enzyme located on the cell surface of lymphocytes and monocytes was to deaminate adenosine, making it less available for uptaking and metabolism, and also for adenosine-receptor activation. Quite unexpectedly, ADA1 was shown to act extraenzymatically. In addition, cell surface ADA1-binding proteins have been identified. Interestingly, the interaction of ADA1 with these anchoring proteins leads to costimulation of T-cell activation. Recent studies performed with professional antigen-presenting cells and T lymphocytes have shown that ADA1 can bridge the two cell types together by a “cross-linking” established between different anchoring molecules in each cell. Some aspects of ADA action are similar to that of growth factors. In fact, ADA1 is a member of the adenosine deaminase growth factor (ADGF) family. Some molecular mechanisms that occur in ADA-related SCID and the role ADA1 may play in acquired immunodeficiency are also reviewed here.