T cells probe a diverse milieu of peptides presented by molecules of the major histocompatibility complex (MHC) by using the T-cell receptor (TCR) to scan these ligands with high sensitivity and specificity. Here we describe a physical basis for this scanning process by studying the residues involved in both the initial association and the stable binding of TCR to peptide-MHC, using the well-characterized TCR and peptide-MHC pair of 2B4 and MCC-IE(k) (moth cytochrome c, residues 88 103). We show that MHC contacts dictate the initial association, guiding TCR docking in a way that is mainly independent of the peptide. Subsequently, MCC-IE(k) peptide contacts dominate stabilization, imparting specificity and influencing T-cell activation by modulating the duration of binding. This functional subdivision of the peptide-MHC ligand suggests that a two-step process for TCR recognition facilitates the efficient scanning of diverse peptide-MHC complexes on the surface of cells and also makes TCRs inherently crossreactive towards different peptides bound by the same MHC.

Patients who develop AKI during a hospitalization are at substantial risk for the development of CKD by 1 year following hospitalization and timing of AKI recovery is a strong predictor, even for the mildest forms of AKI.

Earlier recognition of chronic kidney disease (CKD) could slow progression, prevent complications, and reduce cardiovascular-related outcomes. However, current estimates of CKD awareness indicate that both patient- and provider-level awareness remain unacceptably low. Many of the factors that are possibly associated with CKD awareness, which could help guide implementation of awareness efforts, have yet to be fully examined. Also, little is known regarding whether increased patient or provider awareness improves clinical outcomes or whether there are possible negative consequences of awareness for CKD patients. Further research is necessary to continue to design and refine awareness campaigns aimed at both patients and providers, but there is an immediate need for dissemination of basic CKD information, given both the high prevalence of CKD and its risk factors and the low estimated awareness of CKD.