Crystal structure of a T cell receptor bound to an allogeneic MHC molecule
Jean-Baptiste Reiser1, Claudine Darnault1, Annick Guimezanes2, Claude Grégoire2, Thomas Mosser2, Anne-Marie Schmitt-Verhulst2, Juan Carlos Fontecilla-Camps1, Bernard Malissen2, Dominique Housset1
& Gilbert Mazza2
1
Laboratoire de Cristallographie et Cristallogénèse
des Protéines, Institut de Biologie Structurale J.-P. Ebel, CEA-CNRS-UJF
, 41, rue Jules Horowitz, F-38027
Grenoble Cedex 1, France.
2
Centre d'Immunologie INSERM-CNRS de Marseille-Luminy
, Case 906, F-13288 Marseille Cedex
9, France.
Many T cell receptors (TCRs) that are selected to respond to foreign peptide
antigens bound to self major histocompatibility complex (MHC) molecules are
also reactive with allelic variants of self-MHC molecules. This property,
termed alloreactivity, causes graft rejection and graft-versus-host
disease. The structural features of alloreactivity have yet to be defined.
We now present a basis for this cross-reactivity, elucidated by the crystal
structure of a complex involving the BM3.3 TCR and a naturally processed octapeptide
bound to the H-2Kb allogeneic MHC class I molecule. A distinguishing
feature of this complex is that the eleven-residue-long complementarity-determining
region 3 (CDR3) found in the BM3.3 TCR chain folds away from the peptide
binding groove and makes no contact with the bound peptide, the latter being
exclusively contacted by the BM3.3 CDR3. Our results formally establish
that peptide-specific, alloreactive TCRs interact with allo-MHC in a register
similar to the one they use to contact self-MHC molecules.
chain folds away from the peptide
binding groove and makes no contact with the bound peptide, the latter being
exclusively contacted by the BM3.3 CDR3
. Our results formally establish
that peptide-specific, alloreactive TCRs interact with allo-MHC in a register
similar to the one they use to contact self-MHC molecules.
