Research Group Adnane Achour

Structural bases underlying TCR recognition of an MHC class I molecule in complex with a peptide. Overall view of the same TCR binding to the same class I molecule presenting two different epitopes.
Photo: Renhua Sun. Structural bases underlying TCR recognition of an MHC class I molecule in complex with a peptide. Overall view of the same TCR binding to the same class I molecule presenting two different epitopes.

Research focus

Structural and Biophysical Immunology

Introduction

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.

Team Adnane

Adnane Achour, Professor, Group leader

Xiao Han, PhD, Assistant professor

Benedetta Maria Sala, PhD, Assistant professor

Flavio Salazar-Onfray, Affiliated. Professor in Tumor Immunology. Vice rektor of Universidad de Chile, Santiago de Chile.

Tatyana Sandalova, PhD, Researcher

Tim Schulte, PhD, senior scientist. Affiliated. Presently at the Institute of Molecular and Translational Cardiology, IRCCS Policlinico San Donato, San Donato Milanese, Milano, Italy.

Renhua Sun, PhD, Assistant professor

Key Publications

A Novel mRNA-Mediated and MicroRNA-Guided Approach to Specifically Eradicate Drug-Resistant Hepatocellular Carcinoma Cell Lines by Se-Methylselenocysteine.
Selvam AK, Jawad R, Gramignoli R, Achour A, Salter H, Björnstedt M
Antioxidants (Basel) 2021 Jul;10(7):

Clustering of Major Histocompatibility Complex-Class I Molecules in Healthy and Cancer Colon Cells Revealed from Their Nanomechanical Properties.
Moretti M, La Rocca R, Perrone Donnorso M, Torre B, Canale C, Malerba M, Das G, Sottile R, Garofalo C, Achour A, Kärre K, Carbone E, Di Fabrizio E
ACS Nano 2021 04;15(4):7500-7512

Tuning antiviral CD8 T-cell response via proline-altered peptide ligand vaccination.
Duru AD, Sun R, Allerbring EB, Chadderton J, Kadri N, Han X, Peqini K, Uchtenhagen H, Madhurantakam C, Pellegrino S, Sandalova T, Nygren PÅ, Turner SJ, Achour A
PLoS Pathog 2020 05;16(5):e1008244

The serine protease HtrA plays a key role in heat-induced dispersal of pneumococcal biofilms.
Chao Y, Bergenfelz C, Sun R, Han X, Achour A, Hakansson AP
Sci Rep 2020 12;10(1):22455

IL-15 and CD155 expression regulate LAT expression in murine DNAM1+ NK cells, enhancing their effectors functions.
Luu TT, Wagner AK, Schmied L, Meinke S, Freund JE, Kambayashi T, Ravens I, Achour A, Bernhardt G, Chambers BJ, Höglund P, Kadri N
Eur J Immunol 2020 04;50(4):494-504

Biochemical and biophysical comparison of human and mouse beta-2 microglobulin reveals the molecular determinants of low amyloid propensity.
Achour A, Broggini L, Han X, Sun R, Santambrogio C, Buratto J, Visentin C, Barbiroli A, De Luca CMG, Sormanni P, Moda F, De Simone A, Sandalova T, Grandori R, Camilloni C, Ricagno S
FEBS J 2020 02;287(3):546-560

Proinflammatory Histidyl-Transfer RNA Synthetase-Specific CD4+ T Cells in the Blood and Lungs of Patients With Idiopathic Inflammatory Myopathies.
Galindo-Feria AS, Albrecht I, Fernandes-Cerqueira C, Notarnicola A, James EA, Herrath J, Dastmalchi M, Sandalova T, Rönnblom L, Jakobsson PJ, Fathi M, Achour A, Grunewald J, Malmström V, Lundberg IE
Arthritis Rheumatol 2020 01;72(1):179-191

Interaction With 14-3-3 Correlates With Inactivation of the RIG-I Signalosome by Herpesvirus Ubiquitin Deconjugases.
Gupta S, Ylä-Anttila P, Sandalova T, Achour A, Masucci MG
Front Immunol 2020 ;11():437

Assigned NMR backbone resonances of the ligand-binding region domain of the pneumococcal serine-rich repeat protein (PsrP-BR) reveal a rigid monomer in solution.
Schulte T, Sala BM, Nilvebrant J, Nygren PÅ, Achour A, Shernyukov A, Agback T, Agback P
Biomol NMR Assign 2020 10;14(2):195-200

Glycosylation Tunes Neuroserpin Physiological and Pathological Properties.
Visentin C, Broggini L, Sala BM, Russo R, Barbiroli A, Santambrogio C, Nonnis S, Dubnovitsky A, Bolognesi M, Miranda E, Achour A, Ricagno S
Int J Mol Sci 2020 May;21(9):

Multi-HLA class II tetramer analyses of citrulline-reactive T cells and early treatment response in rheumatoid arthritis.
Gerstner C, Turcinov S, Hensvold AH, Chemin K, Uchtenhagen H, Ramwadhdoebe TH, Dubnovitsky A, Kozhukh G, Rönnblom L, Kwok WW, Achour A, Catrina AI, van Baarsen LGM, Malmström V
BMC Immunol 2020 05;21(1):27

An alpaca nanobody neutralizes SARS-CoV-2 by blocking receptor interaction.
Hanke L, Vidakovics Perez L, Sheward DJ, Das H, Schulte T, Moliner-Morro A, Corcoran M, Achour A, Karlsson Hedestam GB, Hällberg BM, Murrell B, McInerney GM
Nat Commun 2020 09;11(1):4420

SAMHD1 phosphorylation and cytoplasmic relocalization after human cytomegalovirus infection limits its antiviral activity.
De Meo S, Dell'Oste V, Molfetta R, Tassinari V, Lotti LV, Vespa S, Pignoloni B, Covino DA, Fantuzzi L, Bona R, Zingoni A, Nardone I, Biolatti M, Coscia A, Paolini R, Benkirane M, Edfors F, Sandalova T, Achour A, Hiscott J, Landolfo S, Santoni A, Cerboni C
PLoS Pathog 2020 09;16(9):e1008855

B cell alterations during BAFF inhibition with belimumab in SLE.
Ramsköld D, Parodis I, Lakshmikanth T, Sippl N, Khademi M, Chen Y, Zickert A, Mikeš J, Achour A, Amara K, Piehl F, Brodin P, Gunnarsson I, Malmström V
EBioMedicine 2019 Feb;40():517-527

Pneumolysin binds to the mannose receptor C type 1 (MRC-1) leading to anti-inflammatory responses and enhanced pneumococcal survival.
Subramanian K, Neill DR, Malak HA, Spelmink L, Khandaker S, Dalla Libera Marchiori G, Dearing E, Kirby A, Yang M, Achour A, Nilvebrant J, Nygren PÅ, Plant L, Kadioglu A, Henriques-Normark B
Nat Microbiol 2019 01;4(1):62-70

Effect of CTLA4-Ig (abatacept) treatment on T cells and B cells in peripheral blood of patients with polymyositis and dermatomyositis.
Tang Q, Ramsköld D, Krystufkova O, Mann HF, Wick C, Dastmalchi M, Lakshmikanth T, Chen Y, Mikes J, Alexanderson H, Achour A, Brodin P, Vencovsky J, Lundberg IE, Malmström V
Scand J Immunol 2019 Jan;89(1):e12732

Successive crystal structure snapshots suggest the basis for MHC class I peptide loading and editing by tapasin.
Hafstrand I, Sayitoglu EC, Apavaloaei A, Josey BJ, Sun R, Han X, Pellegrino S, Ozkazanc D, Potens R, Janssen L, Nilvebrant J, Nygren PÅ, Sandalova T, Springer S, Georgoudaki AM, Duru AD, Achour A
Proc Natl Acad Sci U S A 2019 03;116(11):5055-5060

Individual and stable autoantibody repertoires in healthy individuals.
Neiman M, Hellström C, Just D, Mattsson C, Fagerberg L, Schuppe-Koistinen I, Gummesson A, Bergström G, Kallioniemi O, Achour A, Sallinen R, Uhlén M, Nilsson P
Autoimmunity 2019 02;52(1):1-11

B cell profiling in malaria reveals expansion and remodelling of CD11c+ B cell subsets.
Sundling C, Rönnberg C, Yman V, Asghar M, Jahnmatz P, Lakshmikanth T, Chen Y, Mikes J, Forsell MN, Sondén K, Achour A, Brodin P, Persson KE, Färnert A
JCI Insight 2019 04;5():

The Complement System Is Essential for the Phagocytosis of Mesenchymal Stromal Cells by Monocytes.
Gavin C, Meinke S, Heldring N, Heck KA, Achour A, Iacobaeus E, Höglund P, Le Blanc K, Kadri N
Front Immunol 2019 ;10():2249

14-3-3 scaffold proteins mediate the inactivation of trim25 and inhibition of the type I interferon response by herpesvirus deconjugases.
Gupta S, Ylä-Anttila P, Sandalova T, Sun R, Achour A, Masucci MG
PLoS Pathog 2019 11;15(11):e1008146