| Title | Identification of monoclonal antibody epitopes and critical residues for rhinovirus binding in domain 1 of intercellular adhesion molecule 1. | ||
| Author | McClelland, A; deBear, J; Yost, S C; Meyer, A M; Marlor, C W; Greve, J M | ||
| Journal | Proc Natl Acad Sci U S A | Publication Year/Month | 1991-Sep |
| PMID | 1716769 | PMCID | PMC52431 |
| Affiliation | 1.Molecular Therapeutics, Inc., Miles Research Center, West Haven, CT 06516. | ||
Intercellular adhesion molecule 1 (ICAM-1) is the cellular receptor for the major group of human rhinoviruses (HRVs) and the adhesion ligand of lymphocyte function-associated antigen 1. Analysis of a series of chimeric exchanges between human and murine ICAM-1 shows that two distinct epitopes recognized by monoclonal antibodies that block rhinovirus attachment and cell adhesion map to the N-terminal first domain of ICAM-1. Furthermore the specificity for HRV binding is entirely contained within the first 88 amino acids. Mutagenesis of the four sites of N-linked glycosylation within the second domain shows that carbohydrate is not involved in virus recognition. Homologue replacement mutagenesis localizes the epitopes for virus-blocking antibodies to two regions of domain 1 predicted to form beta strand D and the loop between the F and G strands of an immunoglobulin-fold structure. Analysis of virus binding to the mutants predicts a large surface of contact between HRV and ICAM-1 domain 1 but shows that the regions most important for virus binding are coincident with the monoclonal antibody epitopes.