Deciphering and predicting CD4+ T cell immunodominance of influenza virus hemagglutinin
| Autor: | David J. M. Lewis, Antonio Lanzavecchia, Philipp Carl Georg Paparoditis, Federica Sallusto, Ramgopal R. Mettu, Marco Benevento, Antonino Cassotta, Alessia Donati, Roger Geiger, Samuel J. Landry, Mathilde Foglierini |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
CD4-Positive T-Lymphocytes Receptors Antigen T-Cell alpha-beta Immunology Hemagglutinin (influenza) Hemagglutinin Glycoproteins Influenza Virus Immunodominance Biology Article Infectious Disease and Host Defense 03 medical and health sciences Epitopes 0302 clinical medicine Antigen Influenza Human medicine Immunology and Allergy Cytotoxic T cell Humans Antigen processing Immunodominant Epitopes T-cell receptor High-Throughput Nucleotide Sequencing T-Lymphocytes Helper-Inducer Virology 030104 developmental biology medicine.anatomical_structure Influenza A virus biology.protein Antibody Memory T cell Immunologic Memory 030215 immunology |
| Zdroj: | The Journal of Experimental Medicine Journal of Experimental Medicine, 217 (10) |
| ISSN: | 1540-9538 0022-1007 1540-0069 |
| Popis: | The importance of CD4+ T helper (Th) cells is well appreciated in view of their essential role in the elicitation of antibody and cytotoxic T cell responses. However, the mechanisms that determine the selection of immunodominant epitopes within complex protein antigens remain elusive. Here, we used ex vivo stimulation of memory T cells and screening of naive and memory T cell libraries, combined with T cell cloning and TCR sequencing, to dissect the human naive and memory CD4+ T cell repertoire against the influenza pandemic H1 hemagglutinin (H1-HA). We found that naive CD4+ T cells have a broad repertoire, being able to recognize naturally processed as well as cryptic peptides spanning the whole H1-HA sequence. In contrast, memory Th cells were primarily directed against just a few immunodominant peptides that were readily detected by mass spectrometry–based MHC-II peptidomics and predicted by structural accessibility analysis. Collectively, these findings reveal the presence of a broad repertoire of naive T cells specific for cryptic H1-HA peptides and demonstrate that antigen processing represents a major constraint determining immunodominance. Journal of Experimental Medicine, 217 (10) ISSN:0022-1007 ISSN:1540-0069 ISSN:1540-9538 |
| Databáze: | OpenAIRE |
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