T cells use their T‐cell receptors (TCRs) to discriminate between lower‐affinity self and higher‐affinity foreign peptide major‐histocompatibility‐complexes (pMHCs) based on the TCR/pMHC off‐rate. It is now appreciated that T cells generate mechanical forces during this process but how force impacts the TCR/pMHC off‐rate remains debated. Here, we measured the effect of mechanical force on the off‐rate of multiple TCR/pMHC interactions. Unexpectedly, we found that lower‐affinity TCR/pMHCs with faster solution off‐rates were more resistant to mechanical force (weak slip or catch bonds) than higher‐affinity interactions (strong slip bonds). This was confirmed by molecular dynamics simulations. Consistent with these findings, we show that the best‐characterized catch bond, involving the OT‐I TCR, has a low affinity and an exceptionally fast solution off‐rate. Our findings imply that reducing forces on the TCR/pMHC interaction improves antigen discrimination, and we suggest a role for the adhesion receptors CD2 and LFA‐1 in force‐shielding the TCR/pMHC interaction.

Background: Periodontal disease can lead to bacteremia with release of cytokines, affecting implantation in women trying to conceive through in vitro fertilization (IVF). A potential association between maternal periodontal disease and poor IVF outcomes has been described. Objective: The aim of the study is to assess whether pre-existing periodontal disease has any effect on IVF parameters. Method: A pilot study composed of 34 women was conducted at a tertiary care center. Prior to IVF, dental examination, IVF parameters were collected. Results: Thirty-four women participated in the study. The outcomes of 28 women (82.3%) were analyzed. Out of the 28 patients, 17 patients had a positive pregnancy test (60.7%) with a total of 13 live births (46.4%) and 4 pregnancy losses (14.3%). Plaque and bleeding index scores were both lower in patients who achieved pregnancy after IVF yet did not reach statistical significance ( p =0.309 and 0.422). Comparison of mean values for the different infertility parameters showed no significant differences among women with different IVF outcomes ( p >0.05). Different degrees of inflammation of the gingiva did not have an effect on the different clinical parameters and the live birth rates. Conclusion: The evidence provided by the present study does not support the hypothesis. Addressing the status of oral health before any infertility treatment remains to be elucidated.

T cells use their T cell receptors (TCRs) to discriminate between lower-affinity self and higher-affinity foreign peptide major-histocompatibility-complexes (pMHCs) based on the TCR/pMHC off-rate. It is now appreciated that T cells generate mechanical forces during this process but how force impacts the TCR/pMHC off-rate remains unclear. Here, we measured the effect of mechanical force on the off-rate of multiple TCR/pMHC interactions. Unexpectedly, we found that lower-affinity pMHCs with faster solution off-rates were more resistant to mechanical force (weak slip or catch bonds) than higher-affinity interactions (strong slip bonds), and this was confirmed by molecular dynamic simulations. Consistent with these findings, we show that the best characterized catch-bond, involving the OT-I TCR, has a low affinity and an exceptionally fast solution off-rate. Our findings imply that reducing forces on the TCR/pMHC interaction improves antigen discrimination and we suggest this new force-shielding role for the adhesion receptors CD2 and LFA-1.