Molecular modeling of a T-cell receptor bound to a major histocompatibility complex molecule: implications for T-cell recognition.
The main functions of the T-cell receptor (TCR) involve its specific interaction with short and linear antigenic peptides bound to the major histocompatibility complex (MHC) molecules. In the absence of a 3D structure for TCR and for the TCR/peptide/MHC complex, several attempts to characterize the structural components of the TCR/peptide/MHC interaction have been made. However, this subject is still troublesome. In this paper a computer-based 3D model for a TCR/peptide/MHC complex (5C.C7/moth cytochrome c [MCC] peptide 93-103/I-Ek) was obtained. The complex surface shows a high complementarity between the 5C.C7 structure and the peptide/I-Ek molecule. The mapping of residues involved in the TCR/peptide/MHC interaction shows close agreement with mutational experiments (Jorgensen JL, Reay PA, Ehrich EW, Davis MM, 1992b, Annu Rev Immunol 10:835-873). Moreover, the results are consistent with a recent variability analysis of TCR sequences using three variability indexes (Almagro JC, Zenteno-Cuevas R, Vargas-Madrazo E, Lara-Ochoa F, 1995b, Int J Pept Protein Res 45:180-186). Accordingly, the 3D model of the 5C.C7/MCC peptide 93-103/I-Ek complex provides a framework to generate testable hypotheses about TCR recognition. Thus, starting from this model, the role played by each loop that forms the peptide/MHC binding site of the TCR is discussed.
Instituto de Química, Universidad Nacional Autónoma de México, Ciudad Universitaria, México, D.F.
J C
JC
Almagro
E
E
Vargas-Madrazo
F
F
Lara-Ochoa
E
E
Horjales
D000595:Amino Acid Sequence; D000818:Animals; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D003574:Cytochrome c Group / Q000378:metabolism; D006680:HLA Antigens / Q000737:chemistry / Q000378:metabolism*; D015798:HLA-DR1 Antigen / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D006860:Hydrogen Bonding; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009036:Moths / Q000737:chemistry; D010446:Peptide Fragments / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000737:chemistry* / Q000378:metabolism*; D016415:Sequence Alignment; D013601:T-Lymphocytes / Q000276:immunology*
D003574:Cytochrome c Group; D006680:HLA Antigens; D015798:HLA-DR1 Antigen; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell