Implications of a Fab-like structure for the T-cell receptor.
The antigen-specific receptor of T lymphocytes (TCR) and the Fab moiety of immunoglobulins are expected to fold into similar three-dimensional structures because of their identical protein domain organization, the conservation of key residues and their overall sequence homology. However, T cells mostly appear to recognize short peptide antigens bound to MHC class I or class II presenting molecules. A complete model of the human leucocyte antigen molecule (HLA-A2) reconstructed from the alpha-carbon coordinates was used to investigate the putative organization of a TCR/peptide/HLA-A2 complex. In this article, Jean-Michel Claverie and co-workers show that the respective geometries of a Fab-like TCR structure and of the HLA-A2 antigen binding site suggest a model where the third variable regions of both chains of the TCR mainly interact with the peptide antigen, while the first and/or second less variable regions are in position for making contact with residues pointing up from the alpha 1 and alpha 2 helical regions of the HLA-A2 molecule.
Claverie
J M
JM
Prochnicka-Chalufour
A
A
Bougueleret
L
L
D000595:Amino Acid Sequence; D001665:Binding Sites; D015234:HLA-A Antigens / Q000378:metabolism; D015789:HLA-A2 Antigen; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D011487:Protein Conformation; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D012689:Sequence Homology, Nucleic Acid; D013329:Structure-Activity Relationship
D015234:HLA-A Antigens; D015789:HLA-A2 Antigen; D007140:Immunoglobulin Fab Fragments; D011948:Receptors, Antigen, T-Cell