Analysis of Qa-1bPeptide Binding Specificity and the Capacity of Cd94/Nkg2a to Discriminate between Qa-1–Peptide Complexes

The major histocompatibility complex class Ib protein, Qa-1b, serves as a ligand for murine CD94/NKG2A natural killer (NK) cell inhibitory receptors. The Qa-1b peptide-binding site is predominantly occupied by a single nonameric peptide, Qa-1 determinant modifier (Qdm), derived from the leader sequence of H-2D and L molecules. Five anchor residues were identified in this study by measuring the peptide-binding affinities of substituted Qdm peptides in experiments with purified recombinant Qa-1b. A candidate peptide-binding motif was determined by sequence analysis of peptides eluted from Qa-1 that had been folded in the presence of random peptide libraries or pools of Qdm derivatives randomized at specific anchor positions. The results indicate that Qa-1b can bind a diverse repertoire of peptides but that Qdm has an optimal primary structure for binding Qa-1b. Flow cytometry experiments with Qa-1b tetramers and NK target cell lysis assays demonstrated that CD94/NKG2A discriminates between Qa-1b complexes containing peptides with substitutions at nonanchor positions P4, P5, or P8. Our findings suggest that it may be difficult for viruses to generate decoy peptides that mimic Qdm and raise the possibility that competitive replacement of Qdm with other peptides may provide a novel mechanism for activation of NK cells

A novel category of antigens enabling CTL immunity to tumor escape variants: Cinderella antigens

Deficiencies in MHC class I antigen presentation are a common feature of tumors and allows escape from cytotoxic T lymphocyte (CTL)-mediated killing. It is crucial to take this capacity of tumors into account for the development of T-cell-based immunotherapy, as it may strongly impair their effectiveness. A variety of escape mechanisms has been described thus far, but progress in counteracting them is poor. Here we review a novel strategy to target malignancies with defects in the antigenic processing machinery (APM). The concept is based on a unique category of CD8+ T-cell epitopes that is associated with impaired peptide processing, which we named TEIPP. We characterized this alternative peptide repertoire emerging in MHC-I on tumors lacking classical antigen processing due to defects in the peptide transporter TAP (transporter associated with peptide processing). These TEIPPs exemplify interesting parallels with the folktale figure Cinderella: they are oppressed and neglected by a stepmother (like functional TAP prevents TEIPP presentation), until the suppression is released and Cinderella/TEIPP achieves unexpected recognition. TEIPP-specific CTLs and their cognate peptide-epitopes provide a new strategy to counteract immune evasion by APM defects and bear potential to targeting escape variants observed in a wide range of cancers

Interest of neural networks for the optimization of the crossflow filtration process

International audienceIn order to build up a model representing the effect of transmembrane pressure and crossflow velocity on crossflow filtration results at quasi-steady state, an approach based on neural networks is proposed. For filtralions of various products (raw cane sugar remelt, natural gum solution) on different membranes (micro- and ultrafiltralion) with or without co-current permeate flow, the modelling of both permeate flux and retention rate could be obtained after only five experimental trials. Compared to more classical modelling techniques, the neural networks were showed to be sometimes better suited and are useful when the effects of hydrodynamical conditions on filtration results are strongly nonlinear. Thanks to established models, it was possible to determine, with a good safety margin, an optimum region in every case studied

Strategy for economical optimisation of the clarification of pulpy fruit juices using crossflow microfiltration

International audienc

Predictive control of a crossflow microfiltration process

Predictive control of a crossflow microfiltration process. Annual meeting of the Institute of Food Technologists (IFT'99

Commande prédictive non-linéaire d'un pilote de microfiltration tangentielle

Jean-Jacques Bimbenet, Coordinateur ; Gilles Muratet, CoordinateurCommande prédictive non-linéaire d'un pilote de microfiltration tangentielle. 6. Congrès français de génie des procédé

Co-immobilized pectinlyase and endocellulase on chitin and Nylon supports

International audienc