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Characterization of IgD-binding by respiratory pathogens.

Samuelsson, Martin LU (2006) In Doctoral Dissertation Series 2006:143.
Abstract
The focus of this thesis was to explore the interaction between IgD and Moraxella catarrhalis and Haemophilus influenzae. These two respiratory pathogens are responsible for otitis media in children, and exacerbations in patients afflicted with predisposing conditions such as chronic obstructive pulmonary disease (COPD). Both M. catarrhalis and H. influenzae have been shown to bind IgD in a non-immune manner. The binding of IgD by M. catarrhalis is mediated through Moraxella IgD-binding protein MID, whereas the IgD receptor on H. influenzae is not yet identified. The region of MID that interacts with IgD has previously been mapped to reside within amino acids 962-1200 (MID962-1200). A consequence of an IgD binding phenotype is the ability... (More)
The focus of this thesis was to explore the interaction between IgD and Moraxella catarrhalis and Haemophilus influenzae. These two respiratory pathogens are responsible for otitis media in children, and exacerbations in patients afflicted with predisposing conditions such as chronic obstructive pulmonary disease (COPD). Both M. catarrhalis and H. influenzae have been shown to bind IgD in a non-immune manner. The binding of IgD by M. catarrhalis is mediated through Moraxella IgD-binding protein MID, whereas the IgD receptor on H. influenzae is not yet identified. The region of MID that interacts with IgD has previously been mapped to reside within amino acids 962-1200 (MID962-1200). A consequence of an IgD binding phenotype is the ability to activate B cells, and in this study we found that purified MID962-1200 had the capacity to activate B cells without the physical presence of T cells. In addition, we showed that for efficient B cell activation, the addition of the cytokines IL-4 or IL-2 was necessary. Furthermore, since MID has a unique specificity for IgD, we were able to use MID to selectively purify IgD from human serum.



To in detail characterize the site on the IgD molecule responsible for the interaction with M. catarrhalis and H. influenzae, we manufactured a series of recombinant IgD molecules. Upon replacement of IgD with corresponding IgG sequences, we were able to determine that the IgD CH1 region contained the binding site for both species. In addition, we determined that IgD CH1 amino acids 198-224 were the interacting residues and that amino acids 198-206 were crucial for the interaction.



In conclusion, the work presented in this thesis shows that the MID protein is capable of activating B cells without T cell help, and that it accomplishes this by binding to IgD CH1 amino acids 198-224. H. influenzae displays a similar IgD binding pattern as MID, and therefore the proteins may be similar. In addition, we developed a novel technique to selectively purify IgD from human serum by the use of recombinant MID. (Less)
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author
supervisor
opponent
  • Professor Sandlie, Inger, University of Oslo
organization
publishing date
type
Thesis
publication status
published
subject
keywords
virology, mycology, H. influenzae, bacteriology, Microbiology, IgD-binding, M. catarrhalis, Mikrobiologi, bakteriologi, virologi, mykologi
in
Doctoral Dissertation Series
volume
2006:143
pages
100 pages
publisher
Medical Microbiology, Lund University
defense location
Patologens Föreläsningssal Ing 78 Mas Malmö
defense date
2006-12-14 09:00:00
ISSN
1652-8220
ISBN
91-85559-65-2
language
English
LU publication?
yes
additional info
T Nordström, J Jendholm, M Samuelsson, A Forsgren and K Riesbeck. 2006. The IgD-binding domain of the Moraxella IgD-binding protein MID (MID962-1200) activates human B cells in the presence of T cell cytokines. Journal of Leukocyte Biology, vol 79 pp 319-329.
M Samuelsson, J Jendholm, S Amisten, S.L Morrison, A Forsgren and K Riesbeck. 2006. The IgD CH1 region contains the binding site for the human respiratory pathogen Moraxella catarrhalis IgD-binding protein MID. European Journal of Immunology, vol 36 pp 2525-2534.
M Samuelsson, A Forsgren and K Riesbeck. 2006. Purification of IgD from human serum – a novel application of recombinant M. catarrhalis IgD binding protein MID. Journal of Immunological Methods, (inpress)
M Samuelsson, A Forsgren and K Riesbeck. . Characterization of the IgDbinding site of encapsulated Haemophilus influenzae serotype b. (manuscript)
id
690906a3-2dcb-4657-b965-6f02258a799e (old id 547683)
date added to LUP
2016-04-01 16:14:17
date last changed
2019-05-21 13:16:14
@phdthesis{690906a3-2dcb-4657-b965-6f02258a799e,
  abstract     = {{The focus of this thesis was to explore the interaction between IgD and Moraxella catarrhalis and Haemophilus influenzae. These two respiratory pathogens are responsible for otitis media in children, and exacerbations in patients afflicted with predisposing conditions such as chronic obstructive pulmonary disease (COPD). Both M. catarrhalis and H. influenzae have been shown to bind IgD in a non-immune manner. The binding of IgD by M. catarrhalis is mediated through Moraxella IgD-binding protein MID, whereas the IgD receptor on H. influenzae is not yet identified. The region of MID that interacts with IgD has previously been mapped to reside within amino acids 962-1200 (MID962-1200). A consequence of an IgD binding phenotype is the ability to activate B cells, and in this study we found that purified MID962-1200 had the capacity to activate B cells without the physical presence of T cells. In addition, we showed that for efficient B cell activation, the addition of the cytokines IL-4 or IL-2 was necessary. Furthermore, since MID has a unique specificity for IgD, we were able to use MID to selectively purify IgD from human serum.<br/><br>
<br/><br>
To in detail characterize the site on the IgD molecule responsible for the interaction with M. catarrhalis and H. influenzae, we manufactured a series of recombinant IgD molecules. Upon replacement of IgD with corresponding IgG sequences, we were able to determine that the IgD CH1 region contained the binding site for both species. In addition, we determined that IgD CH1 amino acids 198-224 were the interacting residues and that amino acids 198-206 were crucial for the interaction.<br/><br>
<br/><br>
In conclusion, the work presented in this thesis shows that the MID protein is capable of activating B cells without T cell help, and that it accomplishes this by binding to IgD CH1 amino acids 198-224. H. influenzae displays a similar IgD binding pattern as MID, and therefore the proteins may be similar. In addition, we developed a novel technique to selectively purify IgD from human serum by the use of recombinant MID.}},
  author       = {{Samuelsson, Martin}},
  isbn         = {{91-85559-65-2}},
  issn         = {{1652-8220}},
  keywords     = {{virology; mycology; H. influenzae; bacteriology; Microbiology; IgD-binding; M. catarrhalis; Mikrobiologi; bakteriologi; virologi; mykologi}},
  language     = {{eng}},
  publisher    = {{Medical Microbiology, Lund University}},
  school       = {{Lund University}},
  series       = {{Doctoral Dissertation Series}},
  title        = {{Characterization of IgD-binding by respiratory pathogens.}},
  volume       = {{2006:143}},
  year         = {{2006}},
}