MHC2-SCALE enhances identification of immunogenic neoantigens
Summary: Recent studies suggest that CD4+ T cells can exert potent anti-tumor effects and improve immunotherapy efficacy by aiding CD8+ T cells. However, characterizing the mechanism of CD4+ T cells’ anti-tumor activity has been challenging due to inaccurate major histocompatibility complex class II...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-04-01
|
| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004225004730 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850260225820459008 |
|---|---|
| author | Joshua G. Gober Aude-Hélène Capietto Reyhane Hoshyar Martine Darwish Richard Vandlen Jonathan L. Linehan Lélia Delamarre Adel M. ElSohly |
| author_facet | Joshua G. Gober Aude-Hélène Capietto Reyhane Hoshyar Martine Darwish Richard Vandlen Jonathan L. Linehan Lélia Delamarre Adel M. ElSohly |
| author_sort | Joshua G. Gober |
| collection | DOAJ |
| description | Summary: Recent studies suggest that CD4+ T cells can exert potent anti-tumor effects and improve immunotherapy efficacy by aiding CD8+ T cells. However, characterizing the mechanism of CD4+ T cells’ anti-tumor activity has been challenging due to inaccurate major histocompatibility complex class II (MHC-II) peptide prediction algorithms and the lack of high-quality reagents for immune monitoring. To address this, we developed MHC2—substitution of CLIP and analytical LCMS evaluation (MHC2-SCALE), a streamlined approach combining affinity optimized class II-associated invariant chain peptide (CLIP) exchange technology, high throughput 2D-LCMS analysis, and rapid generation of peptide-bound MHC-II monomers for subsequent multimer assembly. We validated MHC-II peptide candidates predicted by the immune epitope database (IEDB) algorithm, as well as uncovered many true and immunogenic MHC-II binders that were not predicted by IEDB. Thus, MHC2-SCALE expands the opportunities for discovering, tracking, and phenotyping antigen-specific CD4+ T cells in preclinical and clinical settings, thereby improving therapies for cancer, autoimmunity, or infectious diseases. |
| format | Article |
| id | doaj-art-df286200c40e4e12a49df22ade8a0a5d |
| institution | OA Journals |
| issn | 2589-0042 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj-art-df286200c40e4e12a49df22ade8a0a5d2025-08-20T01:55:41ZengElsevieriScience2589-00422025-04-0128411221210.1016/j.isci.2025.112212MHC2-SCALE enhances identification of immunogenic neoantigensJoshua G. Gober0Aude-Hélène Capietto1Reyhane Hoshyar2Martine Darwish3Richard Vandlen4Jonathan L. Linehan5Lélia Delamarre6Adel M. ElSohly7Department of Protein Chemistry, Genentech Inc, South San Francisco, CA, USACancer Immunology Department, Genentech Inc, South San Francisco, CA, USACancer Immunology Department, Genentech Inc, South San Francisco, CA, USADepartment of Protein Chemistry, Genentech Inc, South San Francisco, CA, USADepartment of Protein Chemistry, Genentech Inc, South San Francisco, CA, USACancer Immunology Department, Genentech Inc, South San Francisco, CA, USACancer Immunology Department, Genentech Inc, South San Francisco, CA, USADepartment of Protein Chemistry, Genentech Inc, South San Francisco, CA, USA; Department of Immunology Discovery, Genentech Inc, South San Francisco, CA, USA; Corresponding authorSummary: Recent studies suggest that CD4+ T cells can exert potent anti-tumor effects and improve immunotherapy efficacy by aiding CD8+ T cells. However, characterizing the mechanism of CD4+ T cells’ anti-tumor activity has been challenging due to inaccurate major histocompatibility complex class II (MHC-II) peptide prediction algorithms and the lack of high-quality reagents for immune monitoring. To address this, we developed MHC2—substitution of CLIP and analytical LCMS evaluation (MHC2-SCALE), a streamlined approach combining affinity optimized class II-associated invariant chain peptide (CLIP) exchange technology, high throughput 2D-LCMS analysis, and rapid generation of peptide-bound MHC-II monomers for subsequent multimer assembly. We validated MHC-II peptide candidates predicted by the immune epitope database (IEDB) algorithm, as well as uncovered many true and immunogenic MHC-II binders that were not predicted by IEDB. Thus, MHC2-SCALE expands the opportunities for discovering, tracking, and phenotyping antigen-specific CD4+ T cells in preclinical and clinical settings, thereby improving therapies for cancer, autoimmunity, or infectious diseases.http://www.sciencedirect.com/science/article/pii/S2589004225004730Biological sciencesBiochemistry methodsImmunologyProteomics |
| spellingShingle | Joshua G. Gober Aude-Hélène Capietto Reyhane Hoshyar Martine Darwish Richard Vandlen Jonathan L. Linehan Lélia Delamarre Adel M. ElSohly MHC2-SCALE enhances identification of immunogenic neoantigens iScience Biological sciences Biochemistry methods Immunology Proteomics |
| title | MHC2-SCALE enhances identification of immunogenic neoantigens |
| title_full | MHC2-SCALE enhances identification of immunogenic neoantigens |
| title_fullStr | MHC2-SCALE enhances identification of immunogenic neoantigens |
| title_full_unstemmed | MHC2-SCALE enhances identification of immunogenic neoantigens |
| title_short | MHC2-SCALE enhances identification of immunogenic neoantigens |
| title_sort | mhc2 scale enhances identification of immunogenic neoantigens |
| topic | Biological sciences Biochemistry methods Immunology Proteomics |
| url | http://www.sciencedirect.com/science/article/pii/S2589004225004730 |
| work_keys_str_mv | AT joshuaggober mhc2scaleenhancesidentificationofimmunogenicneoantigens AT audehelenecapietto mhc2scaleenhancesidentificationofimmunogenicneoantigens AT reyhanehoshyar mhc2scaleenhancesidentificationofimmunogenicneoantigens AT martinedarwish mhc2scaleenhancesidentificationofimmunogenicneoantigens AT richardvandlen mhc2scaleenhancesidentificationofimmunogenicneoantigens AT jonathanllinehan mhc2scaleenhancesidentificationofimmunogenicneoantigens AT leliadelamarre mhc2scaleenhancesidentificationofimmunogenicneoantigens AT adelmelsohly mhc2scaleenhancesidentificationofimmunogenicneoantigens |