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. 2021 Jul 16;118(29):e2019639118. doi: 10.1073/pnas.2019639118

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Copyright © 2021 the Author(s). Published by PNAS.

This open access article is distributed under Creative Commons Attribution License 4.0 (CC BY).

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Fig. 3. — Theoretical interpretation of the differential focusing effect mediated by CD8. Graphical representation of the differential focusing effect based on two key assumptions: 1) functional sensitivity depends nonmonotonically on the TCR/pMHCI dissociation rate; and 2) the pMHCI/CD8 interaction affects the TCR/pMHCI dissociation rate by an invariant factor, equivalent to translation on a logarithmic scale (SI Appendix). (A–C) Modulation of the pMHCI/CD8 interaction moves peptide ligands along this curve, altering the agonist hierarchy as a function of the TCR/pMHCI dissociation rate. (D) A hypothetical ultrastrong pMHCI/CD8 interaction would be expected to reverse the agonist hierarchy from FAT > ELA > 3T to FAT < ELA < 3T.