From genes to proteins: the nonspecific cross-reacting antigens

The existence of nonspecific cross-reacting antigens (NCAs), following their first description by von Kleist, was regarded as a disadvantage for the characterization and determination of carcinoembryonic antigen (CEA) using monoclonal antibodies or antiserum. Nowadays, after identification of a family of genes highly homologous to the CEA gene and some of the corresponding proteins, there is increasing evidence for important roles of these molecules in cell adhesion, bacterial binding, bile acid transport and other functions. For example, rapid up-regulation of the well-established NCAs (NCA-160, NCA-95 and NCA-90) on the surface of neutrophilic granulocytes by different inflammatory agents and the inhibition of binding of these cells to cytokine-activated endothelial cells by antibodies against NCAs are good indications for an important role in granulocyte functions. The presence of a consensus sequence in the cytoplasmic domains of some transmembrane members of the CEA family, which was first described for subunits of signal transduction complexes of the immune system (e.g. B and T cell receptor), also suggests a role in signal transduction. Additionally, using stably transfected cells expressing members of the CEA family, NCAs could be clustered to the 'cluster of differentiation' (CD) CD66a-d, during the recent 5th Leukocyte Typing Workshop. Therefore, further contributions to our knowledge about NCAs can be expected not only from researchers working in the CEA field but also from scientists working with cells of the hematopoietic system.