ORCID Profile
0000-0001-6926-9137
Current Organisation
CNRS en Alpes
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Publisher: The American Association of Immunologists
Date: 15-12-2014
Abstract: The structural rules governing peptide/MHC (pMHC) recognition by T cells remain unclear. To address this question, we performed a structural characterization of several HLA-A2 eptide complexes and assessed in parallel their antigenicity, by analyzing the frequency of the corresponding Ag-specific naive T cells in A2+ and A2- in iduals, as well as within CD4+ and CD8+ subsets. We were able to find a correlation between specific naive T cell frequency and peptide solvent accessibility and/or mobility for a subset of moderately prominent peptides. However, one single structural parameter of the pMHC complexes could not be identified to explain each peptide antigenicity. Enhanced pMHC antigenicity was associated with both highly biased TRAV usage, possibly reflecting favored interaction between particular pMHC complexes and germline TRAV loops, and peptide structural features allowing interactions with a broad range of permissive CDR3 loops. In this context of constrained TCR docking mode, an optimal peptide solvent exposed surface leading to an optimal complementarity with TCR interface may constitute one of the key features leading to high frequency of specific T cells. Altogether our results suggest that frequency of specific T cells depends on the fine-tuning of several parameters, the structural determinants governing TCR–pMHC interaction being just one of them.
Publisher: The American Association of Immunologists
Date: 15-04-2009
Abstract: The di-allelic HLA-A2 restricted minor histocompatibility Ag HA-1 locus codes for the highly immunogenic HA-1His and the nonimmunogenic HA-1Arg nonapeptides, differing in one amino acid. The HA-1His peptide is currently used for boosting the graft-vs-tumor responses after HLA matched HA-1 mismatched stem cell transplantation usage of the HA-1Arg peptide would significantly enlarge the applicability for this therapy. Our studies on mechanisms causing the HA-1 unidirectional immunogenicity revealed marginal differences in proteasomal digestion, TAP translocation, and binding affinity, whereas both dissociation rates and structural analyses clearly showed marked differences in the stability of these two HLA-A2 bound alleles. These data provide a rationale for the lack of HA-1Arg peptide immunogenicity essential for the choice of tumor peptides for stem cell-based immunotherapeutic application.
Publisher: American Society for Microbiology
Date: 03-2009
DOI: 10.1128/EC.00334-08
Abstract: Protein kinase CK2 (casein kinase 2) is a eukaryotic serine/threonine protein kinase with multiple substrates and roles in erse cellular processes, including differentiation, proliferation, and translation. The mammalian holoenzyme consists of two catalytic alpha or alpha′ subunits and two regulatory beta subunits. We report the identification and characterization of a Plasmodium falciparum CK2α orthologue, PfCK2α, and two PfCK2β orthologues, PfCK2β1 and PfCK2β2. Recombinant PfCK2α possesses protein kinase activity, exhibits similar substrate and cosubstrate preferences to those of CK2α subunits from other organisms, and interacts with both of the PfCK2β subunits in vitro. Gene disruption experiments show that the presence of PfCK2α is crucial to asexual blood stage parasites and thereby validate the enzyme as a possible drug target. PfCK2α is amenable to inhibitor screening, and we report differential susceptibility between the human and P. falciparum CK2α enzymes to a small molecule inhibitor. Taken together, our data identify PfCK2α as a potential target for antimalarial chemotherapeutic intervention.
No related grants have been discovered for jean-baptiste reiser.