CD48: A co-stimulatory receptor of immunity

The CD48 molecule is a glycosyl-phosphatidyl-inositol (GPI)-anchored cell-surface protein of the CD2 family of molecules. Originally described on virally-induced B cells, CD48 has been found on various hematopoietic cells, and its expression is regulated by viral and bacterial products and immune-associated proteins. CD48 binds CD2 and other molecules, yet its high-affinity ligand in both mouse and human systems is 2B4. Despite its lack of an intracellular domain, stimulation of CD48 induces rearrangement of signaling factors in lipid rafts, Lck-kinase activity, and tyrosine phosphorylation. As an adhesion and co-stimulatory molecule, CD48 induces numerous effects in B and T lymphocytes, natural killer cells, mast cells, and eosinophils. Some of these depend upon cell-cell interactions via 2B4-CD48 binding. The structural and phenotypic characteristics of CD48, and its role in physiological and pathophysiological processes, are reviewed herein. Possible CD48-based applications for immune-impaired and inflammatory disorders are discussed as well.