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Xeno interactions between MHC-I proteins and molecular chaperones enable ligand exchange on a broad repertoire of HLA allotypes.
Sun, Yi; Papadaki, Georgia F; Devlin, Christine A; Danon, Julia N; Young, Michael C; Winters, Trenton J; Burslem, George M; Procko, Erik; Sgourakis, Nikolaos G.
Afiliación
  • Sun Y; Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
  • Papadaki GF; Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, 3501 Civic Center Blvd., Philadelphia, PA 19104, USA.
  • Devlin CA; Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
  • Danon JN; Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, 3501 Civic Center Blvd., Philadelphia, PA 19104, USA.
  • Young MC; Department of Biochemistry and Cancer Center at Illinois, University of Illinois, Urbana, IL 61820, USA.
  • Winters TJ; Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
  • Burslem GM; Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, 3501 Civic Center Blvd., Philadelphia, PA 19104, USA.
  • Procko E; Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
  • Sgourakis NG; Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, 3501 Civic Center Blvd., Philadelphia, PA 19104, USA.
Sci Adv ; 9(8): eade7151, 2023 02 24.
Article en En | MEDLINE | ID: mdl-36827371
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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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Inmunoglobulinas / Antígenos de Histocompatibilidad Clase I Límite: Humans Idioma: En Revista: Sci Adv Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Inmunoglobulinas / Antígenos de Histocompatibilidad Clase I Límite: Humans Idioma: En Revista: Sci Adv Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos