Novel MHC-Independent αβTCRs Specific for CD48, CD102, and CD155 Self-Proteins and Their Selection in the Thymus
MHC-independent αβTCRs (TCRs) recognize conformational epitopes on native self-proteins and arise in mice lacking both MHC and CD4/CD8 coreceptor proteins. Although naturally generated in the thymus, these TCRs resemble re-engineered therapeutic chimeric antigen receptor (CAR) T cells in their specificity for MHC-independent ligands. Here we identify naturally arising MHC-independent TCRs reactive to three native self-proteins (CD48, CD102, and CD155) involved in cell adhesion. We report that naturally arising MHC-independent TCRs require high affinity TCR-ligand engagements in the thymus to signal positive selection and that high affinity positive selection generates a peripheral TCR repertoire with limited diversity and increased self-reactivity. We conclude that the affinity of TCR-ligand engagements required to signal positive selection in the thymus inversely determines the diversity and self-tolerance of the mature TCR repertoire that is selected.
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REFERENCES
- https://doi.org//10.1016/S0065-2776(01)78004-2
- https://doi.org//10.1038/334395a0
- https://doi.org//10.1016/0092-8674(94)90497-9
- https://doi.org//10.1146/annurev.immunol.21.120601.141107
- https://doi.org//10.1097/TP.0000000000001654
- https://doi.org//10.1038/s41577-018-0007-5
- https://doi.org//10.1146/annurev.immunol.23.021704.115658
- https://doi.org//10.1038/s41467-019-08906-7
- https://doi.org//10.1016/j.it.2012.05.006
- https://doi.org//10.1016/j.immuni.2007.10.007
- https://doi.org//10.1016/j.immuni.2011.11.013
- https://doi.org//10.1016/j.cell.2013.08.009
- https://doi.org//10.1038/46218
- https://doi.org//10.1111/j.1365-2567.2011.03547.x
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AUTHORS (14)
CATEGORIES
- Transplantation Immunology
- Tumour Immunology
- Immunology not elsewhere classified
- Immunology
- Veterinary Immunology
- Animal Immunology
- Genetic Immunology
- Applied Immunology (incl. Antibody Engineering, Xenotransplantation and T-cell Therapies)
- Autoimmunity
- Cellular Immunology
- Humoural Immunology and Immunochemistry
- Immunogenetics (incl. Genetic Immunology)
- Innate Immunity