The peptide editor HLA-DM (DM) catalyzes the exchange of peptides bound to MHC class II molecules within antigen presenting cells by generating a “peptide-receptive” MHC class II conformation (MHCreceptive) to which peptides readily bind and rapidly unbind. While recent work has uncovered the determinants of DM recognition and effector functions, the nature of MHCreceptive and its interaction with DM remains unclear. Here, we show that DM induces but does not stabilize MHCreceptive in the absence of peptides. We demonstrate that DM is out-competed by certain superantigens, and increasing solvent viscosity inhibits DM-induced peptide association. We suggest that DM mediates peptide exchange by interacting transiently and repeatedly with MHC class II molecules, continually generating MHCreceptive. The simultaneous presence of peptide and DM in the milieu is thus crucial for the efficient generation of specific peptide-MHC class II complexes over time.

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Background: We aimed to determine which factors distinguish cardiothoracic (CT) surgeons practicing at the top-ranked US institutions from their peers. Methods: Using online resources, we collected demographics, training information and academic metrics of 694 cardiac (n=489; 70%) and thoracic (n=205; 30%) surgeons practicing at 57 preeminent US institutions, including those with the highest US News & World Report ranking ("top CT centers"). Results: Two hundred and ninety-nine (43.1%) CT surgeons were practicing at the 18 "top CT centers" and had higher academic productivity (publications, citations) than their peers. While there was no difference in the proportion of international medical graduates (IMGs) (21.4% overall) or of surgeons with a PhD degree (9.4% overall) across institutions, the "top CT centers" had a higher proportion of faculty who received their entire CT training abroad (10.4% vs. 5.8%; P=0.038) or at highly-ranked US institutions. Those who published more during their early career years (residency, fellowship and first 5 years as faculty)were more likely to attain academic (professorship) and institutional leadership (division/department chair) positions and to practice at the "top CT centers". Women represented a minority (7.3% overall; 5.1% of cardiac vs. 12.7% of thoracic surgeons, P<0.001), but with growing prevalence among younger faculty and without differences across institutions. Conclusions: CT surgeons of the best US centers have a more international background and received their training at highly-ranked institutions. Early academic productivity is associated with life-long career achievements, with special importance of the first 5 years as faculty. Women represent a growing proportion of the CT surgical workforce.

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