Speculations on sequence homologies between the fibronectin cell-attachment site, major histocompatibility antigens, and a putative AIDS virus polypeptide.

The core of the fibronectin cell-attachment site has been shown 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 alpha 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 (alpha 1 domain) and class II antigens (beta 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 also found in the sequence of a putative polypeptide chain encoded by the HTLVIII/LAV 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.