scholarly journals Predicted epitope binding core motifs and common amino acid polymorphisms distinguish protective- from susceptibility-associated HLA alleles in leishmaniasis

2021 ◽  
Author(s):  
Nicky de Vrij ◽  
Pieter Meysman ◽  
Sofie Gielis ◽  
Wim Adriaensen ◽  
Kris Laukens ◽  
...  
Keyword(s):  
Amino Acid ◽  
Cell Epitope ◽  
Human Leukocyte ◽  
Common Amino Acid ◽  
Leukocyte Antigen ◽  
Susceptibility Factors ◽  
Binding Core ◽  
Epitope Discovery ◽  
Epitope Binding ◽  
Open Access Resource

AbstractSusceptibility for leishmaniasis is largely dependent on genetic- and immune factors of the host. Despite the previously described association of human leukocyte antigen (HLA) gene cluster variants as genetic susceptibility factors, little is known on the mechanisms that mediate these associations. To characterize the functionality underpinning these associations between HLA and disease, we predicted the epitope binding repertoires for all known leishmaniasis-associated HLA variants collected in a thorough literature review. We identified several amino acid polymorphisms in the HLA sequences that distinguished protective-from risk-associated HLA-DRB1 alleles. Proteome-wide and multi-species T cell epitope binding predictions were carried out across these alleles, enabling us to map the effects on the epitope binding repertoires. The protective-associated HLA-DRB1 alleles were characterized by common binding core motifs, which map to the identified amino acid polymorphisms. These results strongly suggest that polymorphism in the HLA region, 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, of which a set of 14 HLA-unrestricted strong-binding epitopes, conserved across species, were prioritized for further epitope discovery in the search for novel subunit-based vaccines.

scholarly journals HLA-DRB1 Alleles Associated with Lower Leishmaniasis Susceptibility Share Common Amino Acid Polymorphisms and Epitope Binding Repertoires

Vaccines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 270
Author(s):  
Nicky de Vrij ◽  
Pieter Meysman ◽  
Sofie Gielis ◽  
Wim Adriaensen ◽  
Kris Laukens ◽  
...  
Keyword(s):  
Amino Acid ◽  
Cell Epitope ◽  
Human Leukocyte ◽  
Leishmania Species ◽  
Hla Polymorphism ◽  
Common Amino Acid ◽  
Binding Core ◽  
Epitope Discovery ◽  
Epitope Binding ◽  
The Impact

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.

A Systematic Review and Meta-Analysis of HLA-Class-II Associations in Patients with IgG4 Autoimmunity

2021 ◽  
Author(s):  
Anja Panhuber ◽  
Giovanni Lamorte ◽  
Veronica Bruno ◽  
Hakan Cetin ◽  
Wolfgang Bauer ◽  
...  
Keyword(s):  
Systematic Review ◽  
Autoimmune Diseases ◽  
Genetic Risk ◽  
Meta Analysis ◽  
Human Leukocyte ◽  
Pemphigus Vulgaris ◽  
Case Control ◽  
Case Control Studies ◽  
Leukocyte Antigen ◽  
Susceptibility Factors

Abstract Autoimmune diseases caused by pathogenic IgG4 subclass autoantibodies (IgG4-AID) include diseases like MuSK myasthenia gravis, pemphigus vulgaris or thrombotic thrombocytopenic purpura. Their etiology is still unknown. Polymorphisms in the human leukocyte antigen (HLA) gene locus, particularly in HLA-DRB1, are known genetic susceptibility factors for autoimmune diseases. We hypothesized a similar role for HLA polymorphisms in IgG4-AID and conducted a systematic review and meta-analysis with case-control studies on IgG4-AID based on MOOSE/ HuGENet guidelines. Genotype (G) and allele (A) frequencies of HLA-DQB1*05 (G: OR 3.8; 95% CI 2.44-5.9; p < 0.00001; A: OR 2.54; 95% CI 1.82-3.55; p < 0.00001) and HLA-DRB1*14 (G: OR 4.31; 95% CI 2.82-6.59; p < 0.00001; A: OR 4.78; 95% CI 3.52-6.49; p < 0.00001) and the HLA-DRB1*14-DQB1*05 haplotype (OR 6.3; 95% CI 3.28-12.09; p < 0.00001 / OR 4.98; 95% CI 3.8-6.53; p < 0.00001) were increased while HLA-DRB1*13 (G: OR 0.48; 95% CI 0.34-0.68; p < 0.0001; A: OR 0.46; 95% CI 0.34-0.62; p < 0.00001) was decreased in IgG4-AID patients. In conclusion, the HLA-DQB1*05, HLA-DRB1*14 alleles and the HLA-DQB1*05-DRB1*14 haplotype could be genetic risk factors that predispose for the production of pathogenic IgG4 autoantibodies and the HLA-DRB1*13 allele may protect from IgG4 autoimmunity.

scholarly journals HATK: HLA analysis toolkit

2020 ◽  
Author(s):  
Wanson Choi ◽  
Yang Luo ◽  
Soumya Raychaudhuri ◽  
Buhm Han
Keyword(s):  
Amino Acid ◽  
Fine Mapping ◽  
Disease Susceptibility ◽  
Human Leukocyte ◽  
Amino Acid Sequences ◽  
Hla Typing ◽  
Amino Acid Residues ◽  
Leukocyte Antigen ◽  
Mapping Analysis ◽  
Visualization Tools

Abstract Summary Fine-mapping human leukocyte antigen (HLA) genes involved in disease susceptibility to individual alleles or amino acid residues has been challenging. Using information regarding HLA alleles obtained from HLA typing, HLA imputation or HLA inference, our software expands the alleles to amino acid sequences using the most recent IMGT/HLA database and prepares a dataset suitable for fine-mapping analysis. Our software also provides useful functionalities, such as various association tests, visualization tools and nomenclature conversion. Availability and implementation https://github.com/WansonChoi/HATK.

scholarly journals The human leukocyte antigen (HLA)-C-specific "activatory" or "inhibitory" natural killer cell receptors display highly homologous extracellular domains but differ in their transmembrane and intracytoplasmic portions.

1996 ◽  
Vol 183 (2) ◽  
pp. 645-650 ◽  
Author(s):  
R Biassoni ◽  
C Cantoni ◽  
M Falco ◽  
S Verdiani ◽  
C Bottino ◽  
...  
Keyword(s):  
Amino Acid ◽  
Human Leukocyte Antigen ◽  
Natural Killer ◽  
Killer Cell ◽  
Human Leukocyte ◽  
Receptor Activation ◽  
Leukocyte Antigen ◽  
Allele Specificity ◽  
Specific Receptors ◽  
Activation Motif

Natural killer cells express clonally distributed receptors specific for major histocompatibility complex class I molecules. The human leukocyte antigen (HLA)-C-specific receptors have been molecularly identified and cloned. They exist not only as inhibitory (p58) but also as activatory (p50) receptors. Here we show that p50 and p58 are highly homologous in their extracellular regions formed by two Ig-like domains. In contrast, major differences exist in their transmembrane and cytoplasmic portions. Whereas p 58 displays a 76-84-amino acid cytoplasmic tail containing an unusual antigen receptor activation motif, p50 is characterized by a shorter 39-amino acid tail. In addition, whereas p58 has a nonpolar transmembrane portion, p50 contains the charged amino acid Lys. These data strongly suggest that receptors with identical HLA-C allele specificity can mediate functions of opposite sign owing to their different transmembrane/cytoplasmic portions.

Human Leukocyte Antigen Class II Amino Acid Epitopes

2002 ◽  
Vol 165 (6) ◽  
pp. 788-794 ◽  
Author(s):  
MILTON D. ROSSMAN ◽  
JOSE STUBBS ◽  
CHUNG WHA LEE ◽  
ELIAS ARGYRIS ◽  
ELENI MAGIRA ◽  
...  
Keyword(s):  
Amino Acid ◽  
Human Leukocyte Antigen ◽  
Human Leukocyte Antigen Class ◽  
Human Leukocyte ◽  
Class Ii ◽  
Leukocyte Antigen

scholarly journals Protective effect of human leukocyte antigen B27 in hepatitis C virus infection requires the presence of a genotype-specific immunodominant CD8+ T-cell epitope

Hepatology ◽  
2009 ◽  
Vol 51 (1) ◽  
pp. 54-62 ◽  
Author(s):  
Christoph Neumann-Haefelin ◽  
Jörg Timm ◽  
Julia Schmidt ◽  
Nadine Kersting ◽  
Karen Fitzmaurice ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Virus Infection ◽  
Protective Effect ◽  
Cell Epitope ◽  
Human Leukocyte ◽  
Cd8 T Cell ◽  
T Cell Epitope ◽  
Hepatitis C Virus Infection ◽  
Leukocyte Antigen

The new human leukocyte antigen-A*2631 is characterized by a new HLA-A polymorphism at amino acid position 62

2006 ◽  
Vol 68 (4) ◽  
pp. 344-345 ◽  
Author(s):  
A. Balas ◽  
F. Sánchez-Gordo ◽  
C. Hernández-Lamas ◽  
F. García-Sánchez ◽  
J. L. Vicario
Keyword(s):  
Amino Acid ◽  
Human Leukocyte Antigen ◽  
Human Leukocyte ◽  
Amino Acid Position ◽  
Leukocyte Antigen ◽  
Antigen A

Induction of cytotoxic T-cell responses against immunoglobulin V region–derived peptides modified at human leukocyte antigen–A2 binding residues

Blood ◽  
2001 ◽  
Vol 98 (10) ◽  
pp. 2999-3005 ◽  
Author(s):  
Sabine Harig ◽  
Mathias Witzens ◽  
Angela M. Krackhardt ◽  
Andreas Trojan ◽  
Patrick Barrett ◽  
...  
Keyword(s):  
Amino Acid ◽  
Human Leukocyte Antigen ◽  
Binding Affinity ◽  
Mhc Class I ◽  
Human Leukocyte ◽  
Leukocyte Antigen ◽  
Native Peptide ◽  
Binding Residues ◽  
V Region ◽  
Heteroclitic Peptides

Abstract Cytotoxic T-lymphocyte (CTL) responses can be generated against peptides derived from the immunoglobulin (Ig) V region in some but not all patients. The main reason for this appears to be the low peptide-binding affinity of Ig-derived peptides to major histocompatibility complex (MHC) class I molecules and their resulting low immunogenicity. This might be improved by conservative amino acid modifications at the MHC-binding residues of the peptides (heteroclitic peptides). In this study, it was found that in 18 Ig-derived peptides, that heteroclitic peptides from the Ig gene with improved binding to human leukocyte antigen (HLA)-A*0201 can be used to improve CTL responses. Amino acid substitution substantially increased predicted binding affinity, and there was a strong correlation between predicted and actual binding to HLA-A*0201. CTLs generated against the heteroclitic peptide had not only enhanced cytotoxicity against the heteroclitic peptide but also increased killing of antigen-presenting cells pulsed with the native peptide. Surprisingly, no difference was observed in the frequency of T cells detected by MHC class I peptide tetramers after stimulation with the heteroclitic peptide compared with the native peptide. CTLs generated against heteroclitic peptides could kill patients' tumor cells, showing that Ig-derived peptides can be presented by the tumor cell and that the failure to mount an immune response (among other reasons) likely results from the low immunogenicity of the native Ig-derived peptide. These results suggest that heteroclitic Ig-derived peptides can enhance immunogenicity, thereby eliciting immune responses, and that they might be useful tools for enhancing immunotherapy approaches to treating B-cell malignant diseases.

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