The IPD-IMGT/HLA Database

Barker, Dominic J; Maccari, Giuseppe; Georgiou, Xenia; Cooper, Michael A.; Flicek, Paul; Robinson, James T.; Marsh, S. G. E.

doi:10.1093/nar/gkac1011

Cited by 764 publications

(825 citation statements)

References 55 publications

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“…Notably, the CEDAR authors consulted cancer immunology experts before designing the new user interface and the new database will significantly support resurgent interest in antigen-based immunotherapies. Also in the immunology area, the new PGG.MHC database ( 61 ) majors on the population genetics of HLA, especially in Asia; while updates from the heavily used IPD-IMGT/HLA include a refreshed website ( 62 ). Other major resources updating include Ensembl ( 63 ), the UCSC Genome Browser ( 64 ) and GWAS Central ( 65 ).…”

Section: New and Updated Databasesmentioning

confidence: 99%

The 2023 Nucleic Acids Research Database Issue and the online molecular biology database collection

Rigden

Fernández

2023

Nucleic Acids Research

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The 2023 Nucleic Acids Research Database Issue contains 178 papers ranging across biology and related fields. There are 90 papers reporting on new databases and 82 updates from resources previously published in the Issue. Six more papers are updates from databases most recently published elsewhere. Major nucleic acid databases reporting updates include Genbank, ENA, ChIPBase, JASPAR, mirDIP and the Issue's first Breakthrough Article, NACDDB for Circular Dichroism data. Updates from BMRB and RCSB cover experimental protein structural data while AlphaFold 2 computational structure predictions feature widely. STRING and REBASE are stand-out updates in the signalling and enzymes section. Immunology-related databases include CEDAR, the second Breakthrough Article, for cancer epitopes and receptors alongside returning IPD-IMGT/HLA and the new PGG.MHC. Genomics-related resources include Ensembl, GWAS Central and UCSC Genome Browser. Major returning databases for drugs and their targets include Open Targets, DrugCentral, CTD and Pubchem. The EMPIAR image archive appears in the Issue for the first time. The entire database Issue is freely available online on the Nucleic Acids Research website (https://academic.oup.com/nar). The NAR online Molecular Biology Database Collection has been updated, revisiting 463 entries, adding 92 new resources and eliminating 96 discontinued URLs so bringing the current total to 1764 databases. It is available at http://www.oxfordjournals.org/nar/database/c/.

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Section: New and Updated Databasesmentioning

confidence: 99%

The 2023 Nucleic Acids Research Database Issue and the online molecular biology database collection

Rigden

Fernández

2023

Nucleic Acids Research

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“…The classical HLA loci (human leukocyte antigen, the human MHC) encode the most variable proteins in the human genome with more than 35,000 alleles ( 14 ). Polymorphic residues in the HLA peptide–binding groove define a unique peptide repertoire displayed by each allotype ( 15 ), enabling species adaptability to emerging infections.…”

Section: Introductionmentioning

confidence: 99%

Xeno interactions between MHC-I proteins and molecular chaperones enable ligand exchange on a broad repertoire of HLA allotypes

et al. 2023

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Immunological chaperones tapasin and TAP binding protein, related (TAPBPR) play key roles in antigenic peptide optimization and quality control of nascent class I major histocompatibility complex (MHC-I) molecules. The polymorphic nature of MHC-I proteins leads to a range of allelic dependencies on chaperones for assembly and cell-surface expression, limiting chaperone-mediated peptide exchange to a restricted set of human leukocyte antigen (HLA) allotypes. Here, we demonstrate and characterize xeno interactions between a chicken TAPBPR ortholog and a complementary repertoire of HLA allotypes, relative to its human counterpart. We find that TAPBPR orthologs recognize empty MHC-I with broader allele specificity and facilitate peptide exchange by maintaining a reservoir of receptive molecules. Deep mutational scanning of human TAPBPR further identifies gain-of-function mutants, resembling the chicken sequence, which can enhance HLA-A*01:01 expression in situ and promote peptide exchange in vitro. These results highlight that polymorphic sites on MHC-I and chaperone surfaces can be engineered to manipulate their interactions, enabling chaperone-mediated peptide exchange on disease-relevant HLA alleles.

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“…Under physiological conditions, peptide:MHC (pMHC-I) molecules are assembled in the endoplasmic reticulum (ER) and are trafficked to the cell surface to present a pool of millions of different peptides derived from either host (self-peptides) or aberrant proteins, including viral factors and dysregulated oncoproteins (non-self-peptides) ( 2 ). The human MHC-I molecules, referred to as Human Leukocyte Antigens (HLAs), are among the most polymorphic genes with over 35,000 different allotypes reported in the human genome and are classified into the HLA-A , -B , and -C subfamilies ( 6 – 10 ). Several studies have proposed that the vast HLA diversity and extended peptide binding repertoire was driven by evolutionary pressures to adapt in pathogen-rich environments ( 11 – 14 ).…”

Section: Introductionmentioning

confidence: 99%

Decoupling peptide binding from T cell receptor recognition with engineered chimeric MHC-I molecules

et al. 2023

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Major Histocompatibility Complex class I (MHC-I) molecules display self, viral or aberrant epitopic peptides to T cell receptors (TCRs), which employ interactions between complementarity-determining regions with both peptide and MHC-I heavy chain ‘framework’ residues to recognize specific Human Leucocyte Antigens (HLAs). The highly polymorphic nature of the HLA peptide-binding groove suggests a malleability of interactions within a common structural scaffold. Here, using structural data from peptide:MHC-I and pMHC:TCR structures, we first identify residues important for peptide and/or TCR binding. We then outline a fixed-backbone computational design approach for engineering synthetic molecules that combine peptide binding and TCR recognition surfaces from existing HLA allotypes. X-ray crystallography demonstrates that chimeric molecules bridging divergent HLA alleles can bind selected peptide antigens in a specified backbone conformation. Finally, in vitro tetramer staining and biophysical binding experiments using chimeric pMHC-I molecules presenting established antigens further demonstrate the requirement of TCR recognition on interactions with HLA framework residues, as opposed to interactions with peptide-centric Chimeric Antigen Receptors (CARs). Our results underscore a novel, structure-guided platform for developing synthetic HLA molecules with desired properties as screening probes for peptide-centric interactions with TCRs and other therapeutic modalities.

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The IPD-IMGT/HLA Database

Cited by 764 publications

References 55 publications

The 2023 Nucleic Acids Research Database Issue and the online molecular biology database collection

The 2023 Nucleic Acids Research Database Issue and the online molecular biology database collection

Xeno interactions between MHC-I proteins and molecular chaperones enable ligand exchange on a broad repertoire of HLA allotypes

Decoupling peptide binding from T cell receptor recognition with engineered chimeric MHC-I molecules

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