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Citations: 1319
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2021
de Vrij, Nicky; Meysman, Pieter; Gielis, Sofie; Adriaensen, Wim; Laukens, Kris; Cuypers, Bart
HLA-DRB1 Alleles Associated with Lower Leishmaniasis Susceptibility Share Common Amino Acid Polymorphisms and Epitope Binding Repertoires Journal Article
In: Vaccines, vol. 9, no. 3, 2021, ISSN: 2076-393X.
@article{vaccines9030270,
title = {HLA-DRB1 Alleles Associated with Lower Leishmaniasis Susceptibility Share Common Amino Acid Polymorphisms and Epitope Binding Repertoires},
author = {Nicky de Vrij and Pieter Meysman and Sofie Gielis and Wim Adriaensen and Kris Laukens and Bart Cuypers},
url = {https://www.mdpi.com/2076-393X/9/3/270},
doi = {10.3390/vaccines9030270},
issn = {2076-393X},
year = {2021},
date = {2021-01-01},
journal = {Vaccines},
volume = {9},
number = {3},
abstract = {Susceptibility for leishmaniasis is largely dependent on host genetic and immune factors. Despite the previously described association of human leukocyte antigen (HLA) gene cluster variants as genetic susceptibility factors for leishmaniasis, little is known regarding the mechanisms that underpin these associations. To better understand this underlying functionality, we first collected all known leishmaniasis-associated HLA variants in a thorough literature review. Next, we aligned and compared the protection- and risk-associated HLA-DRB1 allele sequences. This identified several amino acid polymorphisms that distinguish protection- from risk-associated HLA-DRB1 alleles. Subsequently, T cell epitope binding predictions were carried out across these alleles to map the impact of these polymorphisms on the epitope binding repertoires. For these predictions, we used epitopes derived from entire proteomes of multiple Leishmania species. Epitopes binding to protection-associated HLA-DRB1 alleles shared common binding core motifs, mapping to the identified HLA-DRB1 amino acid polymorphisms. These results strongly suggest that HLA polymorphism, resulting in differential antigen presentation, affects the association between HLA and leishmaniasis disease development. Finally, we established a valuable open-access resource of putative epitopes. A set of 14 HLA-unrestricted strong-binding epitopes, conserved across species, was prioritized for further epitope discovery in the search for novel subunit-based vaccines.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Susceptibility for leishmaniasis is largely dependent on host genetic and immune factors. Despite the previously described association of human leukocyte antigen (HLA) gene cluster variants as genetic susceptibility factors for leishmaniasis, little is known regarding the mechanisms that underpin these associations. To better understand this underlying functionality, we first collected all known leishmaniasis-associated HLA variants in a thorough literature review. Next, we aligned and compared the protection- and risk-associated HLA-DRB1 allele sequences. This identified several amino acid polymorphisms that distinguish protection- from risk-associated HLA-DRB1 alleles. Subsequently, T cell epitope binding predictions were carried out across these alleles to map the impact of these polymorphisms on the epitope binding repertoires. For these predictions, we used epitopes derived from entire proteomes of multiple Leishmania species. Epitopes binding to protection-associated HLA-DRB1 alleles shared common binding core motifs, mapping to the identified HLA-DRB1 amino acid polymorphisms. These results strongly suggest that HLA polymorphism, resulting in differential antigen presentation, affects the association between HLA and leishmaniasis disease development. Finally, we established a valuable open-access resource of putative epitopes. A set of 14 HLA-unrestricted strong-binding epitopes, conserved across species, was prioritized for further epitope discovery in the search for novel subunit-based vaccines.
Hees, Stijn Van; Cuypers, Bart; Bourgeois, Stefan; Groothuismink, Zwier M A; Meysman, Pieter; der Vlies, Pieter Van; de Knegt, Rob; Vonghia, Luisa; Michielsen, Peter; Francque, Sven; Laukens, Kris; Boonstra, Andre; Vanwolleghem, Thomas
Sorted B cell transcriptomes point towards actively regulated B cell responses during ongoing chronic hepatitis B infections Journal Article
In: Cellular Immunology, vol. 362, pp. 104283, 2021, ISSN: 0008-8749.
@article{VANHEES2021104283,
title = {Sorted B cell transcriptomes point towards actively regulated B cell responses during ongoing chronic hepatitis B infections},
author = {Stijn Van Hees and Bart Cuypers and Stefan Bourgeois and Zwier M A Groothuismink and Pieter Meysman and Pieter Van der Vlies and Rob de Knegt and Luisa Vonghia and Peter Michielsen and Sven Francque and Kris Laukens and Andre Boonstra and Thomas Vanwolleghem},
url = {https://www.sciencedirect.com/science/article/pii/S0008874921000022},
doi = {https://doi.org/10.1016/j.cellimm.2021.104283},
issn = {0008-8749},
year = {2021},
date = {2021-01-01},
journal = {Cellular Immunology},
volume = {362},
pages = {104283},
abstract = {The natural course of chronic hepatitis B virus (HBV) infections follows distinct clinical disease phases, characterized by fluctuating levels of serum HBV DNA and ALT. The immune cells and their features that govern these clinical disease transitions remain unknown. In the current study, we performed RNA sequencing on purified B cells from blood (n = 42) and liver (n = 10) of healthy controls and chronic HBV patients. We found distinct gene expression profiles between healthy controls and chronic HBV patients, as evidenced by 190 differentially expressed genes (DEG), but also between the clinical phenotypes of a chronic HBV infection (17\textendash110 DEG between each phase). Numerous immune pathways, including the B cell receptor pathway were upregulated in liver B cells when compared to peripheral B cells. Further investigation of the detected DEG suggested an activation of B cells during HBeAg seroconversion and an active regulation of B cell signalling in the liver.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
The natural course of chronic hepatitis B virus (HBV) infections follows distinct clinical disease phases, characterized by fluctuating levels of serum HBV DNA and ALT. The immune cells and their features that govern these clinical disease transitions remain unknown. In the current study, we performed RNA sequencing on purified B cells from blood (n = 42) and liver (n = 10) of healthy controls and chronic HBV patients. We found distinct gene expression profiles between healthy controls and chronic HBV patients, as evidenced by 190 differentially expressed genes (DEG), but also between the clinical phenotypes of a chronic HBV infection (17–110 DEG between each phase). Numerous immune pathways, including the B cell receptor pathway were upregulated in liver B cells when compared to peripheral B cells. Further investigation of the detected DEG suggested an activation of B cells during HBeAg seroconversion and an active regulation of B cell signalling in the liver.
2020
Adriaensen, Wim; Cuypers, Bart; Cordero, Carlota F; Mengasha, Bewketu; Blesson, Séverine; Cnops, Lieselotte; Kaye, Paul M; Alves, Fabiana; Diro, Ermias; van Griensven, Johan
Host transcriptomic signature as alternative test-of-cure in visceral leishmaniasis patients co-infected with HIV Journal Article
In: EBioMedicine, vol. 55, 2020, ISSN: 2352-3964.
@article{Adriaensen2020,
title = {Host transcriptomic signature as alternative test-of-cure in visceral leishmaniasis patients co-infected with HIV},
author = {Wim Adriaensen and Bart Cuypers and Carlota F Cordero and Bewketu Mengasha and S\'{e}verine Blesson and Lieselotte Cnops and Paul M Kaye and Fabiana Alves and Ermias Diro and Johan van Griensven},
url = {https://doi.org/10.1016/j.ebiom.2020.102748},
doi = {10.1016/j.ebiom.2020.102748},
issn = {2352-3964},
year = {2020},
date = {2020-05-01},
journal = {EBioMedicine},
volume = {55},
publisher = {Elsevier},
abstract = {BackgroundVisceral leishmaniasis (VL) treatment in HIV patients very often fails and is followed by high relapse and case-fatality rates. Hence, treatment efficacy assessment is imperative but based on invasive organ aspiration for parasite detection. In the search of a less-invasive alternative and because the host immune response is pivotal for treatment outcome in immunocompromised VL patients, we studied changes in the whole blood transcriptional profile of VL-HIV patients during treatment.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BackgroundVisceral leishmaniasis (VL) treatment in HIV patients very often fails and is followed by high relapse and case-fatality rates. Hence, treatment efficacy assessment is imperative but based on invasive organ aspiration for parasite detection. In the search of a less-invasive alternative and because the host immune response is pivotal for treatment outcome in immunocompromised VL patients, we studied changes in the whole blood transcriptional profile of VL-HIV patients during treatment.
2018
Neuter, Nicolas De; Bittremieux, Wout; Beirnaert, Charlie; Cuypers, Bart; Mrzic, Aida; Moris, Pieter; Suls, Arvid; Tendeloo, Viggo Van; Ogunjimi, Benson; Laukens, Kris; Meysman, Pieter
On the feasibility of mining CD8+ T cell receptor patterns underlying immunogenic peptide recognition Journal Article
In: Immunogenetics, vol. 70, no. 3, pp. 159-168, 2018, ISSN: 1432-1211.
@article{DeNeuter2018,
title = {On the feasibility of mining CD8+ T cell receptor patterns underlying immunogenic peptide recognition},
author = {Nicolas De Neuter and Wout Bittremieux and Charlie Beirnaert and Bart Cuypers and Aida Mrzic and Pieter Moris and Arvid Suls and Viggo Van Tendeloo and Benson Ogunjimi and Kris Laukens and Pieter Meysman},
url = {https://doi.org/10.1007/s00251-017-1023-5},
doi = {10.1007/s00251-017-1023-5},
issn = {1432-1211},
year = {2018},
date = {2018-03-01},
journal = {Immunogenetics},
volume = {70},
number = {3},
pages = {159-168},
abstract = {Current T cell epitope prediction tools are a valuable resource in designing targeted immunogenicity experiments. They typically focus on, and are able to, accurately predict peptide binding and presentation by major histocompatibility complex (MHC) molecules on the surface of antigen-presenting cells. However, recognition of the peptide-MHC complex by a T cell receptor (TCR) is often not included in these tools. We developed a classification approach based on random forest classifiers to predict recognition of a peptide by a T cell receptor and discover patterns that contribute to recognition. We considered two approaches to solve this problem: (1) distinguishing between two sets of TCRs that each bind to a known peptide and (2) retrieving TCRs that bind to a given peptide from a large pool of TCRs. Evaluation of the models on two HIV-1, B*08-restricted epitopes reveals good performance and hints towards structural CDR3 features that can determine peptide immunogenicity. These results are of particular importance as they show that prediction of T cell epitope and T cell epitope recognition based on sequence data is a feasible approach. In addition, the validity of our models not only serves as a proof of concept for the prediction of immunogenic T cell epitopes but also paves the way for more general and high-performing models.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Current T cell epitope prediction tools are a valuable resource in designing targeted immunogenicity experiments. They typically focus on, and are able to, accurately predict peptide binding and presentation by major histocompatibility complex (MHC) molecules on the surface of antigen-presenting cells. However, recognition of the peptide-MHC complex by a T cell receptor (TCR) is often not included in these tools. We developed a classification approach based on random forest classifiers to predict recognition of a peptide by a T cell receptor and discover patterns that contribute to recognition. We considered two approaches to solve this problem: (1) distinguishing between two sets of TCRs that each bind to a known peptide and (2) retrieving TCRs that bind to a given peptide from a large pool of TCRs. Evaluation of the models on two HIV-1, B*08-restricted epitopes reveals good performance and hints towards structural CDR3 features that can determine peptide immunogenicity. These results are of particular importance as they show that prediction of T cell epitope and T cell epitope recognition based on sequence data is a feasible approach. In addition, the validity of our models not only serves as a proof of concept for the prediction of immunogenic T cell epitopes but also paves the way for more general and high-performing models.