TY - JOUR T1 - T cells exhibit unexpectedly low discriminatory power and can respond to ultra-low affinity peptide-MHC ligands JF - bioRxiv DO - 10.1101/2020.11.14.382630 SP - 2020.11.14.382630 AU - Johannes Pettmann AU - Enas Abu-Shah AU - Mikhail Kutuzov AU - Daniel B. Wilson AU - Michael L. Dustin AU - Simon J. Davis AU - P. Anton van der Merwe AU - Omer Dushek Y1 - 2020/01/01 UR - http://biorxiv.org/content/early/2020/11/15/2020.11.14.382630.abstract N2 - T cells use their T cell receptors (TCRs) to discriminate between peptide MHC (pMHC) ligands that bind with different affinities but precisely how different remains controversial. This is partly because the affinities of physiologically relevant interactions are often too weak to measure. Here, we introduce a surface plasmon resonance protocol to measure ultra-low TCR/pMHC affinities (KD ~ 1000 μM). Using naïve, memory, and blasted human CD8+ T cells we find that their discrimination power is unexpectedly low, in that they require a large >100-fold decrease in affinity to abolish responses. Interestingly, the discrimination power reduces further when antigen is presented in isolation on artificial surfaces but can be partially restored by adding ligands to CD2 or LFA-1. We were able to fit the kinetic proof-reading model to our data, yielding the first estimates for both the time delay (2.8 s) and number of biochemical steps (2.67). The fractional number of steps suggest that one of the proof-reading steps is not easily reversible.Competing Interest StatementThe authors have declared no competing interest. ER -