Sunday, 17th December 2017

Cell Biology and Immunology

    Organization and function of TCR nanoclusters

 


Grupo-400

 


Hisse Martien van Santen

 ASciStaff

APublications

 

Research interest:

 CBMSOweb 130109HMvS fig-1
Oligomeric TCR complexes at the cell surface of a resting human T cell. Human T cells were fixed and labeled in solution with a monoclonal antibody specific for the TCR-associated CD3 complex and 10 nm gold-conjugated protein A, followed by cell surface replica generation via the freeze-etching technique (in collaboration with the electron microscopy facility of the CBMSO). Replicas were analyzed via TEM at 8K of magnification. Insets show 8-fold enlargements of the indicated areas of the cell. Scale bar in inset: 100 nm.

T lymphocytes recognize pathogen-derived antigenic peptides presented by molecules from the Major Histocompatibility Complex (pMHC) via their T cell antigen receptor (TCR). This recognition event activates the T lymphocytes, which will lead to the unfolding of the adaptive immune response. Despite a relatively low affinity of the TCR for its antigen T lymphocytes are remarkably sensitive and specific, being able to distinguish and become activated by only a few antigenic pMHCs complexes amidst a sea of irrelevant pMHC complexes. One of the underlying reasons for this remarkable property of the T lymphocytes depends on the organization of the TCR at the cell surface membrane. Previous work with the groups of Balbino Alarcón (CBMSO, Madrid) and Wolfgang Schamel (BIOSS, University of Freiburg, Germany) showed that the TCR in resting T cells are grouped in TCR nanoclusters (Schamel et al., 2005) and that this organization in nanoclusters increases the sensitivity of the T lymphocytes (Kumar et al., 2011). We have developed transgenic mouse models with the aim of determining the role of TCR nanoclusters in vaccination, auto-immunity and anti-tumor responses. We are furthermore interested in characterizing the different TCR domains and their post-translational modifications for their role in TCR nanocluster formation. These domains would be attractive targets for small molecular compounds that could reduce or enhance TCR nanocluster formation and hence T lymphocyte sensitivity.


 

Group Members:

  • Hisse M. van Santen (PI)
  • Elena Rodriguez (PhD student)