title: Relation between the heavy chain complementarity region 3 characteristics and rheumatoid factor binding properties.
abstract: Among the rheumatoid factors (RFs), monospecific and polyspecific types can be distinguished. However the molecular basis responsible for their different specificity is not well understood. In a previous report, we have shown that the binding of the majority of the polyspecific antibodies is salt-sensitive. No binding to IgG was observed under high ionic strength (0.3-0.5 M NaCl). This salt-sensitivity was only observed for 18% of the monospecific RFs. Here, we have analyzed 14 RFs representing the 3 different groups (6 salt-insensitive monospecific, 4 salt-sensitive monospecific and 4 salt-sensitive polyspecific RFs). By analysis of the amino acid composition and the distribution of polar and non-polar residues of their heavy chain complementarity-determining region 3 (H-CDR3) in relation to mono/polyspecificity, salt-sensitivity and reactivity against human IgG subclasses, we have identified common structural features responsible for their different binding properties. Salt-sensitive RFs (mono as well as polyspecific antibodies) were characterized by long H-CDR3's (15.3+/-2.7) that contained large numbers of hydrophilic residues such as arginine and serine, while salt-insensitive RFs had more hydrophobic H-CDR3's of smaller length (11.3+/-2.4). In addition, for the monospecific RFs, remarkably similar hydrophilicity H-CDR3 profiles were found that were correlated with their specificity for IgG subclasses. These observations confirm the importance of the H-CDR3 for the binding of RFs to IgG. Furthermore, on the basis of their shorter H-CDR3's and their rather unique H-CDR3 hydrophilicity profiles, it is likely that the majority of the monospecific RFs should be considered as a group of RFs that is independent of the polyspecific RF repertoire.
authors.affiliation: Department of Medicine, University Hospital, Geneva, Switzerland. bas-sylvette@diogenes.hcuge.ch
authors.forename: S
authors.initials: S
authors.lastname: Bas
authors.forename: N
authors.initials: N
authors.lastname: Djavad
authors.forename: J
authors.initials: J
authors.lastname: Schwager
authors.forename: T
authors.initials: T
authors.lastname: Vischer
authors.forename: E
authors.initials: E
authors.lastname: Roosnek
mesh_terms: D000595:Amino Acid Sequence; D000918:Antibody Specificity; D001667:Binding, Competitive; D022801:Complementarity Determining Regions; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000737:chemistry* / Q000276:immunology; D007135:Immunoglobulin Variable Region / Q000737:chemistry* / Q000276:immunology; D007137:Immunoglobulin alpha-Chains / Q000737:chemistry* / Q000276:immunology; D012217:Rheumatoid Factor / Q000737:chemistry* / Q000276:immunology*; D012965:Sodium Chloride / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D022801:Complementarity Determining Regions; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D007137:Immunoglobulin alpha-Chains; D012965:Sodium Chloride; D012217:Rheumatoid Factor