| Autor: |
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 |
| Zdroj: |
Science Immunology; 2019, Vol. 4 Issue 37, p1-13, 13p, 5 Graphs |
| Abstrakt: |
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. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
|
