Identification of monoclonal antibody epitopes and critical residues for rhinovirus binding in domain 1 of intercellular adhesion molecule 1.
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.
McClelland
A
A
Molecular Therapeutics, Inc., Miles Research Center, West Haven, CT 06516.
deBear
J
J
Yost
S C
SC
Meyer
A M
AM
Marlor
C W
CW
Greve
J M
JM
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology; D000956:Antigens, Viral / Q000276:immunology*; D015815:Cell Adhesion Molecules / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D003196:Computer Graphics; D004252:DNA Mutational Analysis; D000939:Epitopes; D006801:Humans; D018799:Intercellular Adhesion Molecule-1; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011991:Receptors, Virus / Q000276:immunology / Q000378:metabolism*; D011993:Recombinant Fusion Proteins; D012229:Rhinovirus / Q000276:immunology*; D013329:Structure-Activity Relationship
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D000956:Antigens, Viral; D015815:Cell Adhesion Molecules; D000939:Epitopes; D011991:Receptors, Virus; D011993:Recombinant Fusion Proteins; D018799:Intercellular Adhesion Molecule-1