IDENTIFICATION OF THE COMPLEMENT IC3B BINDING-SITE IN THE BETA-2 INTEGRIN CR3 (CD11B CD18)/

The divalent cation-dependent interaction of the beta 2 integrin CR3 ( CD11b/CD18) with the major complement opsonic C3 fragment iC3b is an i mportant component of the central role of CR3 in inflammation and immu ne clearance. In this investigation we have identified the iC3b bindin g site in CR3. A recombinant fragment representing the CR3 A domain, a 200-amino acid region in the ectodomain of the CD11b subunit, bound t o iC3b directly and in a divalent cation-dependent manner. The iC3b bi nding site was further localized to a short linear peptide that also b ound iC3b directly and inhibited iC3b binding to the A domain as well as to CR3 expressed by human neutrophils. These data establish a major recognition function for the integrin A-domain and have important imp lications for development of novel antiinflammatory therapeutics.