BETA(2) (CD18) MUTATIONS ABOLISH LIGAND RECOGNITION BY I-DOMAIN INTEGRINS LFA-1 (ALPHA(L)BETA(2), CD11A/CD18) AND MAC-1 (ALPHA(M)BETA(2), CD11B/CD18)

The ''I'' domains of the beta(2) (CD18) leukocyte integrins are implicated in ligand binding function. Moreover, rather than recognizing linear peptide sequences, this class of integrins generally recognizes multiple discontinuous sites on immunoglobulin superfamily adhesion receptors. A conserved cluster of oxygenated residues is involved in ligand recognition by beta(1) and beta(3) integrins. In the present study, we evaluated the role of this region in the I domain-containing beta(2) integrins. Recombinant alpha(L) beta(2) (LFA-1, CD11a/CD18) and alpha(M) beta(2) (MAC-1, CD11b/CD18) were expressed on COS cells, and function was assessed by adhesion to ICAM-1 or iC3b, respectively. Alanine substitution at position Asp(134) or Ser(136) in beta(2) produced a complete loss in the capacity of both alpha(L) beta(2) and alpha(M) beta(2) to support cell adhesion. In contrast, substitution at Asp(128) or Ser(138) resulted in loss of beta(2) surface expression when co-transfected with alpha(L) (CD11a) or alpha(M) (CD11b). These data provide the first evidence for involvement of the beta(2) subunit in ligand binding to I domain integrins.