Frontiers in Immunology (Mar 2024)
Identification of mouse CD4+ T cell epitopes in SARS-CoV-2 BA.1 spike and nucleocapsid for use in peptide:MHCII tetramers
- Laura Bricio-Moreno,
- Laura Bricio-Moreno,
- Laura Bricio-Moreno,
- Juliana Barreto de Albuquerque,
- Juliana Barreto de Albuquerque,
- Juliana Barreto de Albuquerque,
- Jake M. Neary,
- Jake M. Neary,
- Thao Nguyen,
- Thao Nguyen,
- Lucy F. Kuhn,
- Lucy F. Kuhn,
- YeePui Yeung,
- YeePui Yeung,
- Kathryn M. Hastie,
- Sara Landeras-Bueno,
- Eduardo Olmedillas,
- Chitra Hariharan,
- Anusha Nathan,
- Anusha Nathan,
- Matthew A. Getz,
- Alton C. Gayton,
- Ashok Khatri,
- Ashok Khatri,
- Gaurav D. Gaiha,
- Gaurav D. Gaiha,
- Gaurav D. Gaiha,
- Erica Ollmann Saphire,
- Erica Ollmann Saphire,
- Andrew D. Luster,
- Andrew D. Luster,
- Andrew D. Luster,
- James J. Moon,
- James J. Moon,
- James J. Moon,
- James J. Moon
Affiliations
- Laura Bricio-Moreno
- Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Boston, MA, United States
- Laura Bricio-Moreno
- Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Boston, MA, United States
- Laura Bricio-Moreno
- Harvard Medical School, Boston, MA, United States
- Juliana Barreto de Albuquerque
- Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Boston, MA, United States
- Juliana Barreto de Albuquerque
- Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Boston, MA, United States
- Juliana Barreto de Albuquerque
- Harvard Medical School, Boston, MA, United States
- Jake M. Neary
- Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Boston, MA, United States
- Jake M. Neary
- Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Boston, MA, United States
- Thao Nguyen
- Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Boston, MA, United States
- Thao Nguyen
- Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Boston, MA, United States
- Lucy F. Kuhn
- Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Boston, MA, United States
- Lucy F. Kuhn
- Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Boston, MA, United States
- YeePui Yeung
- Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Boston, MA, United States
- YeePui Yeung
- Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Boston, MA, United States
- Kathryn M. Hastie
- Center for Vaccine Innovation, La Jolla Institute for Immunology, La Jolla, CA, United States
- Sara Landeras-Bueno
- Center for Vaccine Innovation, La Jolla Institute for Immunology, La Jolla, CA, United States
- Eduardo Olmedillas
- Center for Vaccine Innovation, La Jolla Institute for Immunology, La Jolla, CA, United States
- Chitra Hariharan
- Center for Vaccine Innovation, La Jolla Institute for Immunology, La Jolla, CA, United States
- Anusha Nathan
- Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, United States
- Anusha Nathan
- Program in Health Sciences and Technology, Harvard Medical School and Massachusetts Institute of Technology, Boston, MA, United States
- Matthew A. Getz
- Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, United States
- Alton C. Gayton
- Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, United States
- Ashok Khatri
- Harvard Medical School, Boston, MA, United States
- Ashok Khatri
- Endocrine Division, MGH, Boston, MA, United States
- Gaurav D. Gaiha
- Harvard Medical School, Boston, MA, United States
- Gaurav D. Gaiha
- Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, United States
- Gaurav D. Gaiha
- Division of Gastroenterology, MGH, Boston, MA, United States
- Erica Ollmann Saphire
- Center for Vaccine Innovation, La Jolla Institute for Immunology, La Jolla, CA, United States
- Erica Ollmann Saphire
- Department of Medicine, University of California San Diego, La Jolla, CA, United States
- Andrew D. Luster
- Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Boston, MA, United States
- Andrew D. Luster
- Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Boston, MA, United States
- Andrew D. Luster
- Harvard Medical School, Boston, MA, United States
- James J. Moon
- Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Boston, MA, United States
- James J. Moon
- Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Boston, MA, United States
- James J. Moon
- Harvard Medical School, Boston, MA, United States
- James J. Moon
- 0Division of Pulmonary and Critical Care Medicine, MGH, Boston, MA, United States
- DOI
- https://doi.org/10.3389/fimmu.2024.1329846
- Journal volume & issue
-
Vol. 15
Abstract
Understanding adaptive immunity against SARS-CoV-2 is a major requisite for the development of effective vaccines and treatments for COVID-19. CD4+ T cells play an integral role in this process primarily by generating antiviral cytokines and providing help to antibody-producing B cells. To empower detailed studies of SARS-CoV-2-specific CD4+ T cell responses in mouse models, we comprehensively mapped I-Ab-restricted epitopes for the spike and nucleocapsid proteins of the BA.1 variant of concern via IFNγ ELISpot assay. This was followed by the generation of corresponding peptide:MHCII tetramer reagents to directly stain epitope-specific T cells. Using this rigorous validation strategy, we identified 6 immunogenic epitopes in spike and 3 in nucleocapsid, all of which are conserved in the ancestral Wuhan strain. We also validated a previously identified epitope from Wuhan that is absent in BA.1. These epitopes and tetramers will be invaluable tools for SARS-CoV-2 antigen-specific CD4+ T cell studies in mice.
Keywords
