A novel Minimalist Cell-Free MHC Class II Antigen Processing System Identifies Immunodominant Epitopes

• Published in: Nature Medicine
• Main Authors: Hartman, Isamu Z., Kim, AeRyon, Cotter, Robert J., Walter, Kimberly, Dalai, Sarat K., Boronina, Tatiana, Griffith, Wendell, Schwenk, Robert, Lanar, David E., Krzych, Urszula, Cole, Robert N., Sadegh-Nasseri, Scheherazade
• Format: Text
• Language: English
• Published: 2010
• Subjects: Article; Avian flu
• Online Access: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3058316; http://www.ncbi.nlm.nih.gov/pubmed/21037588; https://doi.org/10.1038/nm.2248

Immunodominance is defined as restricted responsiveness of T cells to a few selected epitopes from complex antigens. Strategies currently used for elucidating CD4+ T cell epitopes are inadequate. To understand the mechanism of epitope selection for helper T cells, we established a cell-free antigen processing system composed of defined proteins: MHC class II, cathepsins, and HLA-DM. Our minimalist system successfully identified the physiologically selected immunodominant epitopes of model antigens, HA1 from influenza virus (A/Texas/1/77) and type II collagen. When applied for de novo epitope identification to a malaria antigen, or HA1 from H5N1 virus (Avian Flu), the system selected a single epitope from each protein that were confirmed to be immunodominant by their capacity to activate CD4+ T cells in HLA-DR1 positive human volunteers or transgenic mice immunized with the corresponding proteins. Thus, we provide a powerful new tool for the identification of physiologically relevant helper T cell epitopes from antigens.