A novel Minimalist Cell-Free MHC Class II Antigen Processing System Identifies Immunodominant Epitopes
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...
Published in: | Nature Medicine |
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Main Authors: | , , , , , , , , , , , |
Format: | Text |
Language: | English |
Published: |
2010
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Subjects: | |
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 |
Summary: | 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. |
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