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Interplay between superantigens and immunoreceptors

På svenska

Author

Summary, in English

This thesis deals with the interactions between superantigens and their receptors. Superantigens are proteins that are secreted by various bacteria, such as Staphylococcus aureus and Streptococcus pyogenes. Superantigens are able to cross-link T cells and antigen presenting cells by binding to the T cell receptor (TCR) and MHC class II. They bind as unprocessed antigens and activate up to 20 % of all T cells, which leads to release of cytokines, such as IL-2 and IFN-γ, as well as T cell proliferation. To understand how superantigens activate T cells it is important to know how they interact and bind to their receptors. In this work the focus has been on the Staphylococcal enterotoxins (SEs) SEH and SEA. SEA is rather well characterized biologically, while SEH is less characterized. To elucidate how different superantigens may be presented by MHC class II to the T cell the three dimensional structuresof both SEH and a variant of SEA in complex with MHC class II were determined by X-ray crystallography . The structures showed that SEH binds to the β-chain of MHC class II, while SEA is able to bind to both the α-chain and the β-chain. Thus, SEA can cross-link two MHC class II molecules on the APC, which is essential for an optimal T cell activation for SEA. SEH and SEA seem to have a similar way to bind to the β-chain of MHC class II and in both cases it is a zinc dependent interaction of high affinity. Traditionally, superantigens have been known to activate T cells dependent on the Vβ-part of the TCR are therefore said to possess a certain TCRVβ profile. SEH was found to be different since it did not activate T cells dependent on TCRVβ, instead SEH activates T cells dependent on the TCRVα, in particular TCRVα10. This has never been observed for any superantigen before. These new findings change the paradigm on how superantigens activate T cells and also illustrate a much greater biological complexity among superantigens than was previously known.

Publishing year

2003

Language

English

Document type

Dissertation

Publisher

Karin Petersson, Molecular Biophysics, Centre for Chemistry and Chemical engineering, Lund University

Topic

  • Biological Sciences

Keywords

  • serology
  • Immunology
  • TCR
  • MHC class II
  • X-ray crystallography
  • superantigen
  • staphylococcal enterotoxin
  • Biofysik
  • transplantation
  • Immunologi
  • serologi
  • Biophysics

Status

Published

Research group

  • Medical Structural Biology

Supervisor

  • [unknown] [unknown]

ISBN/ISSN/Other

  • ISBN: 91-628-5599-9

Defence date

16 May 2003

Defence time

10:15

Defence place

Room A , Chemical centre

Opponent

  • John D Fraser (Prof.)