Inherent reactivity of unselected TCR repertoires to peptide-MHC molecules
Autor: | Laurent Gapin, S. Harsha Krovi, John W. Kappler, Philippa Marrack |
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Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
chemistry.chemical_classification Multidisciplinary biology Chemistry Repertoire T cell T-cell receptor hemic and immune systems chemical and pharmacologic phenomena Peptide Major histocompatibility complex Germline Cell biology 03 medical and health sciences 030104 developmental biology 0302 clinical medicine medicine.anatomical_structure Antigen Cell culture medicine biology.protein 030215 immunology |
Zdroj: | Proceedings of the National Academy of Sciences. 116:22252-22261 |
ISSN: | 1091-6490 0027-8424 |
Popis: | The repertoire of αβ T cell antigen receptors (TCRs) on mature T cells is selected in the thymus where it is rendered both self-tolerant and restricted to the recognition of major histocompatibility complex molecules presenting peptide antigens (pMHC). It remains unclear whether germline TCR sequences exhibit an inherent bias to interact with pMHC prior to selection. Here, we isolated TCR libraries from unselected thymocytes and upon reexpression of these random TCR repertoires in recipient T cell hybridomas, interrogated their reactivities to antigen-presenting cell lines. While these random TCR combinations could potentially have reacted with any surface molecule on the cell lines, the hybridomas were stimulated most frequently by pMHC ligands. The nature and CDR3 loop composition of the TCRβ chain played a dominant role in determining pMHC-reactivity. Replacing the germline regions of mouse TCRβ chains with those of other jawed vertebrates preserved reactivity to mouse pMHC. Finally, introducing the CD4 coreceptor into the hybridomas increased the proportion of cells that could respond to pMHC ligands. Thus, αβ TCRs display an intrinsic and evolutionary conserved bias for pMHC molecules in the absence of any selective pressure, which is further strengthened in the presence of coreceptors. |
Databáze: | OpenAIRE |
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