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 diff erentiation, affecting cellular communication, signal transduction pat hways and immunological control. This review focuses on the relationsh ips 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 mod ulation of these activities. The discovery of the primary structure ho mology 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-alph a 2 of TM alpha(1) immunomodulating activities create the basis of reH uIFN-alpha therapeutics instead of TM alpha(1) and potentiation of vac cines by reHuIFN-alpha. The first successful attempt at grafting of th e HuIFN-alpha 2's TM alpha(1)-like immunomodulating site to the design ed lie 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 propo sed. The place of IFNs-alpha/beta and their receptors in the hierarchy of cytokines is determined.