Fig. 2: Strengthening force-dependent TCR–pMHC binding through TCR-CDR3α mutagenesis modulates CD8 enhancement power for TCR antigen recognition.
From: TCR catch bonds nonlinearly control CD8 cooperation to shape T cell specificity
a, b Time courses of the H-bond numbers between CDR3α motif of m33- (a) or m67-TCRs (b) and pMHC under cv-SMD simulations, with or without force. c Comparison of the counts of H-bonds, derived from analysis in a, b, in the presence or absence of force by paired t-tests. d, e Zoomed-in structural views of the contact between H-2Kb chain of R4-MHC and CDR3α of m33- (d) or m67-TCRs (e) in cv-SMD simulations, with mutations implemented through energy minimization and RoseTTAFold based on the 2C-TCR–H-2Kb–R4 complex (PDB code: 1G6R). The mutated residues of CDR3α are respectively indicated on the top of each panel, and the H-bonds are indicated by red dashed lines. f–k Force-dependent mean lifetime curves of 2C-, m33- and m67-TCRs interactions with R4- (f–h) or L4-MHCs (i–k), when CD8 is absent or present. The peak bond lifetimes with or without CD8 were statistically analyzed by the Mann–Whitney U-test. The number of bond lifetime measurements per force curve for different TCR–pMHC or TCR–pMHC–CD8 pairs is summarized in Supplementary information, Table S2. All binned data points of force curves are presented as mean ± SEMs and summarized in Supplementary information, Tables S3, S4. Statistical significance was indicated as follows: ns not significant, *P < 0.05, ****P < 0.0001.
