The terminology for both types of structures is shown in Figure 1 and described below. STCRDab is primarily focussed on consistently annotating TCR structural data, but also numbers MHC molecules consistently. Each search generates a unique zip file, containing a summary of the search and Protein Data Bank (PDB) format files of structures that match the query ( 21, 22). Following a query, users can inspect and download individual or sets of TCR structures. STCRDab is linked to SAbDab, so that users can find antibody structures that are similar to TCRs, providing insight into designing TCR-like antibodies and chimaeric antigen receptors. Users can also search by structural annotations, such as the orientation between the TCR’s variable domains ( 20). Users can browse and select both αβ and γδ TCRs based on a wide range of criteria, such as the sequence of the TCR’s complementarity-determining region (CDR) loops, the resolution of the structure, and the type of MHC molecule bound by the TCR. STCRDab is a TCR database that automatically collects and curates data on a weekly basis. We have developed the Structural TCR Database (STCRDab), building on our Structural Antibody Database (SAbDab 19). In addition, IMGT does not allow users to generate bespoke datasets for analysis ( 17). However, it is only possible to search based on a limited set of attributes for example, it is not possible to specify the peptide sequence of the antigen. IMGT ( 17) has a richer (308 experimental structures) and more diverse set of structural data (e.g. Once again like McPAS-TCR, only αβ TCRs are annotated. These structures lack annotations that can be useful for further analyses (e.g. The bulk of the structural data in ATLAS is comprised of homology models of variants of experimental structures. ATLAS is a manually curated database, containing a large volume of affinity data users can view and download one of 87 experimental structures, and retrieve summaries of individual queries. There are two databases that contain some TCR structural information: ATLAS ( 16) and IMGT ( 17). The database does not contain structural information, making it difficult to determine the importance of specific residues in MHC and antigen binding. McPAS-TCR ( 18) is a manually curated database that maps αβ TCR sequences to pathogens or epitopes ( 18). TCR structural data is an invaluable resource for designing and developing computational tools, for example, template-based modelling pipelines ( 12).Ī small number of publicly available databases focus on delivering TCR-specific data ( 16– 18). Given the sensitivity of TCR-MHC interactions and the extreme diversity of the TCR repertoire ( 10, 11), computational methods are increasingly being used for rational TCR design ( 10, 12– 15). The clinical relevance of TCRs has attracted interest in understanding the structural basis of a TCR’s activity ( 7, 8), and exploring the possibility of designing TCRs as novel biotherapeutics ( 9). Upon binding, TCRs can activate the T-cell for direct killing of APCs, or stimulate other components of the adaptive immune system, such as B-cells ( 4– 6). Despite their micromolar binding affinity and potential cross-reactivity, TCRs are selective for foreign peptide-MHC complexes on antigen presenting cells (APCs 1– 3). They are expressed on the surfaces of T-cells and typically recognise peptides that are presented by major histocompatibility complex (MHC) molecules. T-cell receptors (TCRs) are proteins of the adaptive immune response.
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