Isolated hypervariable regions derived from streptococcal M proteins specifically bind human C4b-binding protein: Implications for antigenic variation
Författare
Summary, in English
Antigenic variation in microbial surface proteins represents an apparent paradox, because the variable region must retain an important function, while exhibiting extensive immunological variability. We studied this problem for a group of streptococcal M proteins in which the similar to 50-residue hypervariable regions (HVRs) show essentially no residue identity but nevertheless bind the same ligand, the human complement regulator C4b-binding protein (C4BP). Synthetic peptides derived from different HVRs were found to retain the ability to bind C4BP, implying that the HVR corresponds to a distinct ligand-binding domain that can be studied in isolated form. This finding allowed direct characterization of the ligand-binding properties of isolated HVRs and permitted comparisons between different HV Rs in the absence of conserved parts of the M proteins. Affinity chromatography of human serum on immobilized peptides showed that they bound C4BP with high specificity and inhibition experiments indicated that different peptides bound to the same site in C4BP. Different C4BP-binding peptides did not exhibit any immunological cross-reactivity, but structural analysis suggested that they have similar folds. These data show that the HVR of streptococcal M protein can exhibit extreme variability in sequence and immunological properties while retaining a highly specific ligand-binding function.
Avdelning/ar
Publiceringsår
2001
Språk
Engelska
Sidor
3870-3877
Publikation/Tidskrift/Serie
Journal of Immunology
Volym
167
Issue
7
Dokumenttyp
Artikel i tidskrift
Förlag
American Association of Immunologists
Ämne
- Immunology in the medical area
Aktiv
Published
Forskningsgrupp
- Neuroinflammation
- Host-Pathogen Interactions
ISBN/ISSN/Övrigt
- ISSN: 1550-6606