Interferons alpha/beta and their receptors: place in the hierarchy of cytokines

Interferons alpha/beta (IFNs-alpha/beta) are the first cytokines to be produced by recombinant DNA technology. They regulate growth and differentiation, affecting cellular communication, signal transduction pathways and immunological control. This review focuses on the relationships between the structure and biological activities of IFNs-alpha/beta induced as a result of specific interactions with different types of polypeptide receptors as well as on the role of glycolipids in the modulation of these activities. The discovery of the primary structure homology of HuIFNs-alpha and thymus hormone-thymosin alpha 1 (TM alpha 1), the experimental finding of the competition between IFN-alpha and TM alpha 1 for common receptors and the reproduction by reHuIFN-alpha 2 of TM alpha 1 immunomodulating activities create the basis of reHuIFN-alpha therapeutics instead of TM alpha 1, and potentiation of vaccines by reHuIFN-alpha. The first successful attempt at grafting of the HuIFN-alpha 2s TM alpha 1-like immunomodulating site to the designed de novo protein albeferon is described. This article also aims at reviewing recent data concerning the structure of other cytokines and their receptors. Their reciprocal structure-function taxonomy is proposed. The place of IFNs-alpha/beta and their receptors in the hierarchy of cytokines is determined.