THE I DOMAIN OF INTEGRIN LFA-1 INTERACTS WITH ICAM-1 DOMAIN-1 AT RESIDUE GLU-34 BUT NOT GLN-73

Using a solid phase assay, we show that isolated LFA-1 I domain binds ICAM-1 in a Mg2+-dependent manner and is blocked by anti-I domain mono clonal antibodies. This activity mirrors that of the intact receptor ( Dransfield, I., Cabanas, C., Craig, A., and Hogg, N. (1992) J. Cell Bi ob. 116, 219-226) and suggests that the I domain controls divalent cat ion-dependent receptor function. In ICAM-1, domain 1 residues Glu-34 a nd Gln-73 have been identified as critical for binding of LFA-1 as an intact receptor (Staunton, D. E., Dustin, M. L., Erickson, H. P., and Springer, T. A. (1990) Cell 61, 243-254). For the first time, we show that isolated I domain binds to domain 1 of ICAM-1 and that this inter action is inhibited partially by mutation of Glu-34 but not by Gln-73. The anti-ICAM-1 monoclonal antibody RR1/1, which maps to Gln-73 (Stau nton, D. E., Dustin, M. L., Erickson, H. P., and Springer, T. A. (1990 ) Cell 61, 243-254), enhances I domain binding, suggesting potential a llosteric control or coordinate binding by this region. Finally, I dom ain binding inhibited by Glu-34 ICAM-1 mutation correlates with divale nt cation dependence, indicating that this residue might be in direct contact with the metal ion-dependent adhesion site. Thus, we describe the interaction between the LFA-1 I domain and ICAM-1, an event that c ontrols the function of the intact receptor but includes only part of the complete ligand binding site.