Studies of bacterial surface proteins interacting with the immune system

Henrik G Svensson

Research output: ThesisDoctoral Thesis (compilation)


Pathogenic bacteria express a wide array of surface proteins that interact with the environment. Many of these proteins are believed to be important for the virulence. This thesis deals with the binding of immunoglobulins (Ig) and complement regulating proteins to certain bacterial surface proteins. Protein L from Peptostreptococcus magnus binds to Igk-light chains while protein A from Staphylococcus aureus binds both IgGFc and the variable domain of the Ig heavy chain. To generate a protein capable to bind a wide array of Ig fragments lacking the Fc region we constructed a chimeric protein consisting of the Ig-binding domains from protein L and A. This protein, designated protein LA, retained all the functions of the separate parts and could be used for purification of Ig and Ig fragments. The Ig-binding domain of protein L consists of an a-helix packed on a four stranded b-sheet. To determine which amino acid residues of the Ig-binding domain that are important for binding, 76 variants with single site-specific mutations were generated. When the binding kinetics of these variants were analysed only a small number of the mutants displayed binding kinetics that were different to the original Ig-binding domain. The residues that upon mutation caused a significant change in affinity all clustered in two distinct patches on opposite sides of the protein L module suggesting that a single Ig-binding domain can bind two k-light chains. M proteins are expressed on the surface of group A streptococci (GAS), an important human pathogen, and have for a long time been recognised as important virulence factors. Some M proteins have earlier been shown to interact with factor H (FH) that regulates the activation of the complement system. Here we demonstrate that M proteins also can bind the factor H-like protein-1 (FHL-1), another complement regulatory protein. The interaction was shown to involve the seventh short consensus repeat found in both FH and FHL-1 and two different regions of the M protein were found to be responsible for these interactions. GAS variants that express M proteins deleted for the regions involved in binding of FH and FHL-1 were analysed and it was shown that binding of FH and FHL-1 was not crucial for survival of GAS in blood.
Original languageEnglish
Awarding Institution
  • Division of Microbiology, Immunology and Glycobiology - MIG
  • [unknown], [unknown], Supervisor, External person
Award date2002 Nov 7
ISBN (Print)91-628-5416-X
Publication statusPublished - 2002

Bibliographical note

Defence details

Date: 2002-11-07
Time: 13:15
Place: Rune Grubb-Salen, BMC, Lund

External reviewer(s)

Name: Nygren, Per-Åke
Title: Professor
Affiliation: The Royal Institute of Technology, Stockholm, Sweden


Article: I. Svensson, H. G., Hoogenboom, H. R. and Sjöbring, U. (1998) Protein LA, a novel hybrid protein with unique single-chain Fv antibody- and Fab-binding properties. Eur. J. Biochem. 258:890-896

Article: II. Svensson, H. G., Wedemeyer, W. J., Kortemme, T., Kim, D. E., Sjöbring, U. and Baker, D. Contributions of amino-acid side chains to the kinetics and thermodynamics of the bivalent binding of Protein L to Ig k light chains. Submitted.

Article: III. Kotarsky, H., Hellwage, J., Johnsson, E., Skerka, C., Svensson, H. G., Lindahl, G., Sjöbring, U. and Zipfel, P. F. (1998) Identification of a Domain in Human Factor H-like Protein-1 Required for the Interaction with Streptococcal M Proteins. J. Immunol. 160:3349-3354

Article: IV. Kotarsky, H., Gustafsson, M., Svensson, H. G., Zipfel, P. F., Truedsson, L. and Sjöbring U. (2001) Group A streptococcal phagocytosis resistance is independent of complement factor H and factor H-like protein 1 binding. Mol. Microbiol. 41(4):817-26

Subject classification (UKÄ)

  • Microbiology in the medical area
  • Immunology in the medical area


  • bakteriologi
  • Mikrobiologi
  • virologi
  • mykologi
  • Microbiology
  • bacteriology
  • virology
  • mycology


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