a b s t r a c tBacterial adhesion to biomaterials remains a major problem in the medical devices field. Antimicrobial peptides (AMPs) are well-known components of the innate immune system that can be applied to overcome biofilm-associated infections. Their relevance has been increasing as a practical alternative to conventional antibiotics, which are declining in effectiveness. The recent interest focused on these peptides can be explained by a group of special features, including a wide spectrum of activity, high efficacy at very low concentrations, target specificity, anti-endotoxin activity, synergistic action with classical antibiotics, and low propensity for developing resistance. Therefore, the development of an antimicrobial coating with such properties would be worthwhile. The immobilization of AMPs onto a biomaterial surface has further advantages as it also helps to circumvent AMPs' potential limitations, such as short half-life and cytotoxicity associated with higher concentrations of soluble peptides. The studies discussed in the current review report on the impact of covalent immobilization of AMPs onto surfaces through different chemical coupling strategies, length of spacers, and peptide orientation and concentration. The overall results suggest that immobilized AMPs may be effective in the prevention of biofilm formation by reduction of microorganism survival post-contact with the coated biomaterial. Minimal cytotoxicity and longterm stability profiles were obtained by optimizing immobilization parameters, indicating a promising potential for the use of immobilized AMPs in clinical applications. On the other hand, the effects of tethering on mechanisms of action of AMPs have not yet been fully elucidated. Therefore, further studies are recommended to explore the real potential of immobilized AMPs in health applications as antimicrobial coatings of medical devices.

HFE is a protein known to be involved in iron metabolism; yet, other than its homology with major histocompatibility complex (MHC) class I molecules, it has not been described as having an immunologic function. Here we report that peripheral blood mononuclear cells (PBMCs) from patients with hereditary hemochromatosis (HH) carrying the C282Y mutation in HFE have reduced cell-surface expression of MHC class I due to an enhanced endocytosis rate of MHC class I molecules caused by premature peptide and ␤ 2 -microglobulin dissociation. This faster turnover also leads to increased expression levels of cell-surface free class I heavy chains in mutant PBMCs. Biochemical analysis indicates an earlier peptide loading and endoplasmic reticulum maturation of MHC class I molecules in C282Y mutant cells. Thermostability assays further showed that in HFE mutants the MHC class I peptide loading gives rise to low-stability heterotrimers that dissociate prematurely during its intracellular traffic. The present results suggest the existence of an intriguing cross-talk between a particular HFE mutation and the classical MHC class I route. These findings constitute the first description of peptide presentation pathway abnormalities linked to HFE and provide additional evidence for the occurrence of immunologic defects in patients with HH. IntroductionAntigenic peptides presented by major histocompatibility complex (MHC) class I molecules to CD8 ϩ T cells are mainly derived from proteolysis of newly synthesized proteins in the cytosol 1-3 by the proteasome and TPPII (tripeptidyl-peptidase II). 4 A heterodimer of 2 membrane-spanning molecules, termed TAP1 (transport associated with antigen processing 1) and TAP2, translocates the peptides to the lumen of the endoplasmic reticulum (ER) [5][6][7][8] where they undergo further trimming of their amino-terminal ends by the aminopeptidase ERAAP (aminopeptidase associated with antigen processing in the ER). 9,10 Loading of peptides onto MHC class I molecules involves the formation of a transient protein complex termed the peptide-loading complex (PLC) 11,12 that facilitates the binding of peptide to MHC-␤ 2 -microglobulin (␤ 2 -m) heterodimers. 11 The conformational changes that occur in the newly formed peptide-loaded MHC class I molecules precede their release from the PLC and subsequent delivery to the cell surface via the standard secretory pathway.MHC class I assembly and export from the ER is a complex process 13,14 subjected to a set of quality control mechanisms. This orchestrated process acts concertedly to ensure that high-affinity peptides are loaded onto class I molecules. Tapasin, calreticulin, and ERp57 are some of the key players supposed to take part in this event. 15 Yet the precise mechanisms responsible for optimization of class I maturation and for the prevention of ER escape of premature class I molecules remain to be fully understood.Here, we have studied assembly, peptide loading, and surface expression of MHC class I molecules in peripheral blood mononuclear cells (...