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Mercredi 15 février à 9 heures 30
Dr Stephan GADOLA
Department of Rheumatology and Clinical Immunology,
University of Berne, Switzerland
Recognition of glycolipid antigens by CD1-restricted T-cell
receptors
Invariant human TCR Va24-Ja18+/Vb11+
NKT cells (iNKT) are highly conserved immunoregulatory T-lymphocytes
which are restricted by the non-polymorphic CD1d antigen presenting
molecule. These iNKT have been previously shown to specifically
recognize the CD1d-presented glycolipid a-glycosylceramide
(a-GalCer). The crystal structures and
binding characteristics for one typical iNKT T-cell receptor (TCR),
plus two CD1d/a-GalCer-specific Vb11+
TCRs that use different TCR Va chains,
will be presented. The results illustrate the versatility of the TCR
platform to recognize different species of antigens such as peptides
and glycolipids. A docking model for the TCR - CD1d/a-GalCer
complex will be presented, and its implications for antigen-recognition
by iNKT cells will be discussed. The model supports a diagonal
orientation of TCR on CD1d and suggests that CDR3a,
CDR3b and CDR1b
interact with ligands presented by CD1d, while CDR2b
binds to the CD1d a1-helix. The known
dominant usage of Vb11 and Vb8.2
chains by human and mouse iNKT cells, respectively, for recognition
of CD1d/a-GalCer can be explained in the
light of these results.
Contact :
Luis Garcia-Allès
IPBS , salle de conférence n° 1 , niveau 2
205 route de Narbonne TOULOUSE CEDEX 4 |
Version
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