Unbiased identification of target antigens of CD8+ T cells with combinatorial libraries coding for short peptides
| Autor: | Hartmut Wekerle, Katherina Siewert, Joachim Malotka, Klaus Dornmair, Reinhard Hohlfeld, Naoto Kawakami |
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| Rok vydání: | 2012 |
| Předmět: |
T cell
Receptors Antigen T-Cell Antigen-Presenting Cells chemical and pharmacologic phenomena Computational biology CD8-Positive T-Lymphocytes Major histocompatibility complex General Biochemistry Genetics and Molecular Biology Antigen Peptide Library Chlorocebus aethiops MHC class I medicine Animals Combinatorial Chemistry Techniques Cytotoxic T cell Antigen-presenting cell Genetics biology Histocompatibility Antigens Class I T-cell receptor General Medicine MHC restriction medicine.anatomical_structure COS Cells biology.protein |
| Zdroj: | Nature Medicine. 18:824-828 |
| ISSN: | 1546-170X 1078-8956 |
| DOI: | 10.1038/nm.2720 |
| Popis: | Cytotoxic CD8(+) T cells recognize the antigenic peptides presented by class I major histocompatibility complex (MHC) molecules. These T cells have key roles in infectious diseases, autoimmunity and tumor immunology, but there is currently no unbiased method for the reliable identification of their target antigens. This is because of the low affinities of antigen-specific T cell receptors (TCR) to their target MHC-peptide complexes, the polyspecificity of these TCRs and the requirement that these TCRs recognize protein antigens that have been processed by antigen-presenting cells (APCs). Here we describe a technology for the unbiased identification of the antigenic peptides presented by MHC class I molecules. The technology uses plasmid-encoded combinatorial peptide libraries and a single-cell detection system. We validated this approach using a well-characterized influenza-virus–specific TCR, MHC and peptide combination. Single APCs carrying antigenic peptides can be detected among several million APCs that carry irrelevant peptides. The identified peptide sequences showed a converging pattern of mimotopes that revealed the parent influenza antigen. This technique should be generally applicable to the identification of disease-relevant T cell antigens. |
| Databáze: | OpenAIRE |
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