CDR3 loop flexibility contributes to the degeneracy of TCR recognition.
T cell receptor (TCR) binding degeneracy lies at the heart of several physiological and pathological phenomena, yet its structural basis is poorly understood. We determined the crystal structure of a complex involving the BM3.3 TCR and an octapeptide (VSV8) bound to the H-2K(b) major histocompatibility complex molecule at a 2.7 A resolution, and compared it with the BM3.3 TCR bound to the H-2K(b) molecule loaded with a peptide that has no primary sequence identity with VSV8. Comparison of these structures showed that the BM3.3 TCR complementarity-determining region (CDR) 3alpha could undergo rearrangements to adapt to structurally different peptide residues. Therefore, CDR3 loop flexibility helps explain TCR binding cross-reactivity.
Reiser
Jean-Baptiste
JB
Laboratoire de Cristallographie et Cristallogenèse des Protéines, Institut de Biologie Structurale J.-P. Ebel, CEA-CNRS-UJF, 41 rue Jules Horowitz, F-38027 Grenoble Cedex 1, France.
Darnault
Claudine
C
Grégoire
Claude
C
Mosser
Thomas
T
Mazza
Gilbert
G
Kearney
Alice
A
van der Merwe
P Anton
PA
Fontecilla-Camps
Juan Carlos
JC
Housset
Dominique
D
Malissen
Bernard
B
D022801:Complementarity Determining Regions / Q000737:chemistry* / Q000276:immunology; D006801:Humans; D008024:Ligands; D011485:Protein Binding / Q000276:immunology; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D011948:Receptors, Antigen, T-Cell / Q000737:chemistry* / Q000276:immunology; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000737:chemistry / Q000276:immunology*
D022801:Complementarity Determining Regions; D008024:Ligands; D011948:Receptors, Antigen, T-Cell