A Role for Differential Variable Gene Pairing in Creating T Cell Receptors Specific for Unique Major Histocompatibility Ligands
| Autor: | Priya G. Huseby, Brian D. Stadinski, Lawrence J. Stern, Rebecca Smith, Guoqi Li, Bianca Bautista, Peter Trenh, Eric S. Huseby |
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| Rok vydání: | 2011 |
| Předmět: |
Genetics
0303 health sciences MHC class II biology Immunology T-cell receptor chemical and pharmacologic phenomena Computational biology MHC restriction Major histocompatibility complex Article Histocompatibility 03 medical and health sciences 0302 clinical medicine Infectious Diseases Protein structure MHC class I biology.protein Immunology and Allergy CD8 030304 developmental biology 030215 immunology |
| Zdroj: | Immunity. 35:694-704 |
| ISSN: | 1074-7613 |
| DOI: | 10.1016/j.immuni.2011.10.012 |
| Popis: | Summary A limited set of T cell receptor (TCR) variable (V) gene segments are used to create a repertoire of TCRs that recognize all major histocompatibility complex (MHC) ligands within a species. How individual αβTCRs are constructed to specifically recognize a limited set of MHC ligands is unclear. Here we have identified a role for the differential pairing of particular V gene segments in creating TCRs that recognized MHC class II ligands exclusively, or cross-reacted with classical and nonclassical MHC class I ligands. Biophysical and structural experiments indicated that TCR specificity for MHC ligands is not driven by germline-encoded pairwise interactions. Rather, identical TCRβ chains can have altered peptide-MHC (pMHC) binding modes when paired with different TCRα chains. The ability of TCR chain pairing to modify how V region residues interact with pMHC helps to explain how the same V genes are used to create TCRs specific for unique MHC ligands. |
| Databáze: | OpenAIRE |
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