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Empty peptide-receptive MHC class I molecules for efficient detection of antigen-specific T cells

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Saini, SK, Tamhane, T, Anjanappa, R, Saikia, A, Ramskov, S, Donia, M, Svane, IM, Jakobsen, SN, Garcia-Alai, M, Zacharias, M, Meijers, R, Springer, S & Hadrup, SR 2019, 'Empty peptide-receptive MHC class I molecules for efficient detection of antigen-specific T cells' Nature Immunology, bind 4, nr. 37. https://doi.org/10.1126/sciimmunol.aau9039

APA

CBE

Saini SK, Tamhane T, Anjanappa R, Saikia A, Ramskov S, Donia M, Svane IM, Jakobsen SN, Garcia-Alai M, Zacharias M, Meijers R, Springer S, Hadrup SR. 2019. Empty peptide-receptive MHC class I molecules for efficient detection of antigen-specific T cells. Nature Immunology. 4(37). https://doi.org/10.1126/sciimmunol.aau9039

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Author

Saini, Sunil Kumar ; Tamhane, Tripti ; Anjanappa, Raghavendra ; Saikia, Ankur ; Ramskov, Sofie ; Donia, Marco ; Svane, Inge Marie ; Jakobsen, Søren Nyboe ; Garcia-Alai, Maria ; Zacharias, Martin ; Meijers, Rob ; Springer, Sebastian ; Hadrup, Sine Reker. / Empty peptide-receptive MHC class I molecules for efficient detection of antigen-specific T cells. I: Nature Immunology. 2019 ; Bind 4, Nr. 37.

Bibtex

@article{5c2c9b33192e40bf99a3391c7bce268c,
title = "Empty peptide-receptive MHC class I molecules for efficient detection of antigen-specific T cells",
abstract = "The peptide-dependent stability of MHC class I molecules poses a substantial challenge for their use in peptide-MHC multimer-based approaches to comprehensively analyze T cell immunity. To overcome this challenge, we demonstrate the use of functionally empty MHC class I molecules stabilized by a disulfide bond to link the α1 and α2 helices close to the F pocket. Peptide-loaded disulfide-stabilized HLA-A*02:01 shows complete structural overlap with wild-type HLA-A*02:01. Peptide-MHC multimers prepared using disulfide-stabilized HLA-A*02:01, HLA-A*24:02, and H-2Kb can be used to identify antigen-specific T cells, and they provide a better staining index for antigen-specific T cell detection compared with multimers prepared with wild-type MHC class I molecules. Disulfide-stabilized MHC class I molecules can be loaded with peptide in the multimerized form without affecting their capacity to stain T cells. We demonstrate the value of empty-loadable tetramers that are converted to antigen-specific tetramers by a single-step peptide addition through their use to identify T cells specific for mutation-derived neoantigens and other cancer-associated antigens in human melanoma.",
author = "Saini, {Sunil Kumar} and Tripti Tamhane and Raghavendra Anjanappa and Ankur Saikia and Sofie Ramskov and Marco Donia and Svane, {Inge Marie} and Jakobsen, {S{\o}ren Nyboe} and Maria Garcia-Alai and Martin Zacharias and Rob Meijers and Sebastian Springer and Hadrup, {Sine Reker}",
note = "Copyright {\circledC} 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.",
year = "2019",
month = "7",
day = "19",
doi = "10.1126/sciimmunol.aau9039",
language = "English",
volume = "4",
journal = "Nature Immunology",
issn = "1529-2908",
publisher = "Nature Publishing Group",
number = "37",

}

RIS

TY - JOUR

T1 - Empty peptide-receptive MHC class I molecules for efficient detection of antigen-specific T cells

AU - Saini, Sunil Kumar

AU - Tamhane, Tripti

AU - Anjanappa, Raghavendra

AU - Saikia, Ankur

AU - Ramskov, Sofie

AU - Donia, Marco

AU - Svane, Inge Marie

AU - Jakobsen, Søren Nyboe

AU - Garcia-Alai, Maria

AU - Zacharias, Martin

AU - Meijers, Rob

AU - Springer, Sebastian

AU - Hadrup, Sine Reker

N1 - Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

PY - 2019/7/19

Y1 - 2019/7/19

N2 - The peptide-dependent stability of MHC class I molecules poses a substantial challenge for their use in peptide-MHC multimer-based approaches to comprehensively analyze T cell immunity. To overcome this challenge, we demonstrate the use of functionally empty MHC class I molecules stabilized by a disulfide bond to link the α1 and α2 helices close to the F pocket. Peptide-loaded disulfide-stabilized HLA-A*02:01 shows complete structural overlap with wild-type HLA-A*02:01. Peptide-MHC multimers prepared using disulfide-stabilized HLA-A*02:01, HLA-A*24:02, and H-2Kb can be used to identify antigen-specific T cells, and they provide a better staining index for antigen-specific T cell detection compared with multimers prepared with wild-type MHC class I molecules. Disulfide-stabilized MHC class I molecules can be loaded with peptide in the multimerized form without affecting their capacity to stain T cells. We demonstrate the value of empty-loadable tetramers that are converted to antigen-specific tetramers by a single-step peptide addition through their use to identify T cells specific for mutation-derived neoantigens and other cancer-associated antigens in human melanoma.

AB - The peptide-dependent stability of MHC class I molecules poses a substantial challenge for their use in peptide-MHC multimer-based approaches to comprehensively analyze T cell immunity. To overcome this challenge, we demonstrate the use of functionally empty MHC class I molecules stabilized by a disulfide bond to link the α1 and α2 helices close to the F pocket. Peptide-loaded disulfide-stabilized HLA-A*02:01 shows complete structural overlap with wild-type HLA-A*02:01. Peptide-MHC multimers prepared using disulfide-stabilized HLA-A*02:01, HLA-A*24:02, and H-2Kb can be used to identify antigen-specific T cells, and they provide a better staining index for antigen-specific T cell detection compared with multimers prepared with wild-type MHC class I molecules. Disulfide-stabilized MHC class I molecules can be loaded with peptide in the multimerized form without affecting their capacity to stain T cells. We demonstrate the value of empty-loadable tetramers that are converted to antigen-specific tetramers by a single-step peptide addition through their use to identify T cells specific for mutation-derived neoantigens and other cancer-associated antigens in human melanoma.

U2 - 10.1126/sciimmunol.aau9039

DO - 10.1126/sciimmunol.aau9039

M3 - Journal article

VL - 4

JO - Nature Immunology

JF - Nature Immunology

SN - 1529-2908

IS - 37

ER -

ID: 57727789