The I domains of CD11 are responsible for the binding of ligands and have a unique structure with 6-7 alpha helixes and 6 beta sheets with interconnecting loops. To determine loops recognizing fibrinogen in CD11c I domain, five oligopeptides corresponding to CD11c loops were used to prevent fibrinogen binding to isolated CD11c I domain. The results of the inhibition experiment indicated that all of the loops except the one between E-beta sheet and 6-alpha helix were involved in the binding to fibrinogen. The peptide PDalpha5 and alpha3alpha4 showed higher inhibitory activity than others, and the combination of four peptides blocked fibrinogen binding to the I domain completely. These peptides (betaAalpha1, alpha3alpha4, beta3Dalpha5 and betaFalpha7) could block THP-1 cell binding to fibrinogen coated surface as well. Alanine substitution of amino acids on the I domain such as Y249A and Q201A (which are on the loops betaD-alpha5 and alpha3-alpha4 respectively) abolished fibrinogen binding, while mutation on the loop betaE-alpha6 (Q273A) had no effect on fibrinogen binding. Taken together, the results from this study suggest that the loops on the top of CD11c I domain such as loop betaA-alpha1, alpha3-alpha4, betaD-alpha5 and betaF-alpha7 are involved in fibrinogen binding, and two loops (alpha3-alpha4 and betaD-alpha5) are more important than others for the recognition of fibrinogen. (C) 2002 Elsevier Science (USA).