Novel MHC-Independent αβTCRs Specific for CD48, CD102, and CD155 Self-Proteins and Their Selection in the Thymus

oleh: François Van Laethem, Ingrid Saba, Jinghua Lu, Abhisek Bhattacharya, Xuguang Tai, Terry I. Guinter, Britta Engelhardt, Amala Alag, Mirelle Rojano, Jennifer M. Ashe, Ken-ichi Hanada, James C. Yang, Peter D. Sun, Alfred Singer

Format: Article
Diterbitkan: Frontiers Media S.A. 2020-06-01

Deskripsi

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.