Research Group Adnane Achour
Structural and Biophysical Immunology
Cellular communication is achieved through the interactions of specialized receptor molecules at the cell surface and their ligands. The expertise of the Achour research group is multiple, making use of a combination of structural biology, biophysical characterization and immunology to understand the function of pathogen-derived virulence-associated proteins as well as to define novel procedures that allow for the design of Major Histocompatibility Complex (MHC)-class I and class II-restricted altered peptide ligands. Deep knowledge in molecular biology, biochemistry, X-ray crystallography and Small Angle X-ray Scattering is combined with expertise in functional in vitro and in vivo immunological assays as well as a large panel of different biophysical technologies, including Surface Plasmon Resonance, Isothermal Titration Calorimetry and microscale thermophoresis, to define and study how proteins interact with other ligands, how they manipulate and distort immune responses and finally how one may reestablish efficient immunological responses and/or define novel inhibitors. By understanding the structural details of proteins, we can probe their function and potentially design artificial ligands that could modulate their function and activity. All of our studies are complemented by a wide array of in vitro and in vivo immunological assays.
Major research focus
Development of MHC class I-binding altered peptides for vaccines
Using a combination of structural biology and immunology, our research group has defined a procedure that allows for the design of altered peptide ligands (APLs) that bind with high affinity to MHC-I and MHC-II ligands. The immunogenic APLs act as mimotopes of disease-associated non-immunogenic epitopes, and enhance the stability of MHC-I and MHC-II/peptide complexes. Importantly, these modified peptides conserve a structural conformation similar to the wild-type infection-derived or non-immunogenic tumor-associated peptides. Studies performed within our laboratory demonstrate that the induced immunogenic CD4+ and CD8+ T cells cross-react with the original peptides, resulting in enhanced in vitro and in vivo responses. Studies of the functional and structural consequences of substitutions in APLs on CD8 responses directed towards tumor associated antigens and viral immune escape variants are ongoing. Similarly studies on the initiation of CD4+ T cells using MHC-II-restricted epitopes are also performed in close collaboration with clinical research groups. The effects of similar modifications are also tested on modulation of recognition by natural killer (NK) cells.
Determination of the crystal structures of Streptococcus pneumoniae-associated virulence factors
Streptococcus pneumoniae (pneumococcus) is a major human pathogen and the leading cause of pneumoniae, bacteremia and meningitis in adults. The increasing number of antibiotic-resistant strains and the suboptimal clinical efficacy of available vaccines hamper control of this pathogen. We focus on novel virulence-related pneumococcal proteins that could be used as potential targets for future drugs.
Adnane Achour, Professor, Group leader
Tatyana Sandalova, Senior scientist
Tim Schulte, Post-doc
Angel Vizoso, Vazques, Post-doc
Renhua Sun, Post-doc
Xiao Han, PhD student
Ida Hafstrand, PhD student
Additional Researchers in our Lab:
Anatoly Dubnovitsky, Senior scientist
Christina Gerstner, PhD student
Angeles Galindo, PhD student
The crystal structure of the major pneumococcal autolysin LytA in complex with a large peptidoglycan fragment reveals the pivotal role of glycans for lytic activity.
Mol. Microbiol. 2016 Sep;101(6):954-67
T-cell receptor-HLA-DRB1 associations suggest specific antigens in pulmonary sarcoidosis.
Eur. Respir. J. 2016 Mar;47(3):898-909
TAP-independent self-peptides enhance T cell recognition of immune-escaped tumors.
J. Clin. Invest. 2016 Feb;126(2):784-94
The MHC Class I Cancer-Associated Neoepitope Trh4 Linked with Impaired Peptide Processing Induces a Unique Noncanonical TCR Conformer.
J. Immunol. 2016 Mar;196(5):2327-34
Risk Factors for Postoperative Fibrinogen Deficiency after Surgical Removal of Intracranial Tumors.
PLoS ONE 2015 ;10(12):e0144551
Structural and functional insights into peptidoglycan access for the lytic amidase LytA of Streptococcus pneumoniae.
MBio 2014 Feb;5(1):e01120-13