Speculations on Sequence Homologies Between the Fibronectin Cell-Attachment Site, Major Histocompatibility Antigens, and a Putative AIDS Virus Polypeptide Charles Auffray and Jiri Novotny ABSTRACT: The core of the fibronectin cell-attachment site has beenshown to be the tetrapeptide sequence Arg-Gly-Asp-Ser (RGDS). This peptide as well as its inverted analogue Ser-Asp-Gly-Arg (SDGR) efficiently inhibit fibronectin-mediated cell attachment in vivo and in vitro. Homology searches in protein data banks revealed the presence of the peptide SDGR in the c~2 domain of MHC class I antigens, and a variant of RGDS, Arg-Phe-Asp-Ser (RFDS), was found highly conserved in MHC class I (~1 domain) and class II antigens (~1 domain). Three-dimensional models of MHC class I antigens suggested that the two tetrapeptide sequences may be located at the surface of the molecule, readily available for intermolecular contacts. We propose that fibronectin-mediated and MHC-mediated cell-cell interactions have similar molecular bases and that the RGDS-like sequences participate in specific cell adhesion between lymphoid cells. The RFDS tetrapeptide was alsofound in the sequence of a putative polypeptide chain encodedby the HTLVIII/LA V retrovirus family, the causative agent of AIDS. These amino acid sequence homologies suggest a common molecular basis for specific interactions between the MHC class II antigens, or the AIDS virus. and the T-cell specific T4 glycoprotein. ABBREVIATIONS MHC major histocompatibility complex AIDS acquired immune deficiency syndrome INTRODUCTION Fibronectin is a major component of the extracellular matrix which has been associated with several important biological functions: cell adhesion and spread- ing, cell migration, cytoskeletal organization, hemostasis, thrombosis, and malig- nant transformation. These various properties are mediated by independent struc- tural domains that allow binding of fibronectin to other components of the extracellular matrix and to a receptor located at the surface of most eucaryotic cells [1]. It is by its cell-attachment properties that fibronectin regulates the migratory behavior of eukaryotic cells during the early stages of development. Thus, using anti-fibronectin antibodies, it is possible to inhibit cell migration both in vivo during gastrulation and in vitro on fibronectin-coated surfaces [2,3]. Using From the lnstitut d'Embryologie (CNRS et Coll$ge de FranceJ, Nogent s/Marne, France,"Molecular and Cellular Research Laboratory, Massachusetts General Hospital and Harvard Medical School Boston. Massachusetts. Address correspondence to Charles Auffray. pH.D., 1-Institut d'Embryologie (CNRS et CollSgede France~, 49 bis Avenue de la Belle Gabrielle. 94130 Nogent sur Marne, France. Human Immunology 15, 381-390 (1986) © Elsevier Science Publishing Co., Inc., 1986 52 Vanderbilt Ave., New York, NY 10017 381 0198=8859/86/$3.50