IMGT Standardization for Molecular Characterization of the T-cell Receptor/Peptide/MHC Complexes

Abstract

One of the key elements in the adaptive immune response is the presentation of peptides by the major histocompatibility complex (MHC) to the T-cell receptors (TR) at the surface of T cells. The characterization of the TR/peptide/MHC trimolecular complexes (TR/pMHC) is crucial to the fields of immunology, vaccination, and immunotherapy. In order to facilitate data comparison and cross-referencing between experiments from different laboratories whatever the receptor, the chain type, the domain, or the species, IMGT®, the international ImMunoGeneTics information system® (http://imgt.cines.fr), has developed IMGT-ONTOLOGY, the first ontology in immunogenetics and immunoinformatics. In IMGT/3Dstructure-DB, the IMGT three-dimensional structure database, the molecular characterization of the TR/pMHC is made according to the IMGT Scientific chart rules that are based on the IMGT-ONTOLOGY concepts. IMGT/3Dstructure-DB provides the standardized IMGT gene and allele names (CLASSIFICATION), the standardized IMGT labels (DESCRIPTION), and the IMGT unique numbering (NUMEROTATION). As the IMGT structural unit is the domain, amino acids at conserved positions always have the same number in the IMGT® databases, tools, and Web resources. For the TR α and β chains, the amino acids in contact with the peptide/MHC (pMHC) are defined according to the IMGT unique numbering for V-DOMAIN. The MHC chain cleft that binds the peptide is formed by two groove domains (G-DOMAIN), each one comprising four antiparallel β strands and one α helix. The IMGT unique numbering for G-DOMAIN applies both to the first two domains (G-ALPHA1 and G-ALPHA2) of the MHC class I α chain, and to the first domain (G-ALPHA and G-BETA) of the MHC class II α chain and β chain, respectively. Based on the IMGT unique numbering, we defined 11 contact sites for the analysis of the pMHC contacts. The TR/pMHC contact description, based on the IMGT numbering, can be queried in the IMGT/StucturalQuery tool, at http://imgt.cines.fr.