scholarly journals In silico investigation of binding affinities between human leukocyte antigen class I molecules and SARS-CoV-2 virus spike and ORF1ab proteins

2021 ◽  
Author(s):  
Spyros A. Charonis ◽  
Effie-Photini Tsilibary ◽  
Apostolos P. Georgopoulos
Keyword(s):  
Human Leukocyte Antigen ◽  
In Silico ◽  
Human Leukocyte ◽  
Hla Class I ◽  
Hla Class Ii ◽  
Class I ◽  
Binding Affinities ◽  
S Protein ◽  
Leukocyte Antigen ◽  
Hla Class I Molecules

Aim: The novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019, a global pandemic. There is hence an urgent need for effective approaches to understand the mechanism of viral interaction with immune cells that lead to viral elimination and subsequent long-term immunity. The first, immediate response to the viral infection involves mobilization of native immunity and human leukocyte antigen (HLA) class I mechanisms to kill infected cells and eliminate the virus. The second line of defense involves the activation of HLA class II system for the production of antibodies against the virus which will add to the elimination of the virus and prevent future infections. In a previous study, investigated the relations between SARS-CoV-2 spike glycoprotein (S protein) and HLA class II alleles were investigaed; here report on the relations of the S protein and the open reading frame 1ab (ORF1ab) of SARS-CoV-2 to HLA class I alleles. Methods: An in silico sliding window approach was used to determine exhaustively the binding affinities of linear epitopes of 10 amino acid length (10-mers) to each of 61 common (global frequency ≥ 0.01) HLA class I molecules (17, 24 and 20 from gene loci A, B and C, respectively). A total of 8,354 epitopes were analyzed; 1,263 from the S protein and 7,091 from ORF1ab. Results: HLA-A genes were the most effective at binding SARS-CoV-2 epitopes for both spike and ORF1ab proteins. Good binding affinities were found for all three genes and were distributed throughout the length of the S protein and ORF1ab polyprotein sequence. Conclusions: Common HLA class I molecules, as a population, are very well suited to binding with high affinity to SARS-CoV-2 spike and ORF1ab proteins and hence should be effective in aiding the early elimination of the virus.

scholarly journals A Viral, Transporter Associated with Antigen Processing (TAP)-independent, High Affinity Ligand with Alternative Interactions Endogenously Presented by the Nonclassical Human Leukocyte Antigen E Class I Molecule

2012 ◽  
Vol 287 (42) ◽  
pp. 34895-34903 ◽  
Author(s):  
Elena Lorente ◽  
Susana Infantes ◽  
David Abia ◽  
Eilon Barnea ◽  
Ilan Beer ◽  
...  
Keyword(s):  
Human Leukocyte Antigen ◽  
Antigen Processing ◽  
Human Leukocyte ◽  
Hla Class I ◽  
Class I ◽  
Structural Motif ◽  
Leukocyte Antigen ◽  
High Affinity ◽  
Hla Class I Molecules ◽  
Infected Cells

The transporter associated with antigen processing (TAP) enables the flow of viral peptides generated in the cytosol by the proteasome and other proteases to the endoplasmic reticulum, where they complex with nascent human leukocyte antigen (HLA) class I. Later, these peptide-HLA class I complexes can be recognized by CD8+ lymphocytes. Cancerous cells and infected cells in which TAP is blocked, as well as individuals with unusable TAP complexes, are able to present peptides on HLA class I by generating them through TAP-independent processing pathways. Here, we identify a physiologically processed HLA-E ligand derived from the D8L protein in TAP-deficient vaccinia virus-infected cells. This natural high affinity HLA-E class I ligand uses alternative interactions to the anchor motifs previously described to be presented on nonclassical HLA class I molecules. This octameric peptide was also presented on HLA-Cw1 with similar binding affinity on both classical and nonclassical class I molecules. In addition, this viral peptide inhibits HLA-E-mediated cytolysis by natural killer cells. Comparison between the amino acid sequences of the presenting HLA-E and HLA-Cw1 alleles revealed a shared structural motif in both HLA class molecules, which could be related to their observed similar cross-reactivity affinities. This motif consists of several residues located on the floor of the peptide-binding site. These data expand the role of HLA-E as an antigen-presenting molecule.

scholarly journals SARS-CoV-2 Virus and Human Leukocyte Antigen (HLA) Class II: Investigation in silico of Binding Affinities for COVID-19 Protection and Vaccine Development

2020 ◽  
Vol 4 (4) ◽  
pp. 12-23 ◽  
Author(s):  
Spyros Charonis ◽  
Effie-Photini Tsilibary ◽  
Apostolos Georgopoulos
Keyword(s):  
Human Leukocyte Antigen ◽  
Binding Affinity ◽  
In Silico ◽  
Vaccine Development ◽  
Human Leukocyte ◽  
Class Ii ◽  
Hla Class Ii ◽  
Effective Vaccine ◽  
Binding Affinities ◽  
Leukocyte Antigen

SARS-CoV-2 causes COVID-19, urgently requiring the development of effective vaccine(s). Much of current efforts focus on the SARS-CoV-2 spike-glycoprotein by identifying highly antigenic epitopes as good vaccine candidates. However, high antigenicity is not sufficient, since the activation of relevant T cells depends on the presence of the complex of the antigen with a suitably matching Human Leukocyte Antigen (HLA) Class II molecule, not the antigen alone: in the absence of such a match, even a highly antigenic epitope in vitro will not elicit antibody formation in vivo. Here we assessed systematically in silico the binding affinity of epitopes of the spike-glycoprotein to 66 common HLA-Class-II alleles (frequency ≥ 0.01). We used a sliding epitope window of 22-amino-acid-width to scan the entire protein and determined the binding affinity of each subsequence to each HLA allele. DPB1 had highest binding affinities, followed by DRB1 and DQB1. Higher binding affinities were concentrated in the initial part of the glycoprotein (S1-S460), with a peak at S223-S238. This region would be well suited for effective vaccine development by ensuring high probability for successful matching of the vaccine antigen from that region to a HLA Class II molecule for CD4+ T cell activation by the antigen-HLA molecule complex.

scholarly journals Multiple sclerosis: disease modifying therapy and the human leukocyte antigen

2018 ◽  
Vol 76 (10) ◽  
pp. 697-704 ◽  
Author(s):  
Lineu Cesar Werneck ◽  
Paulo José Lorenzoni ◽  
Cláudia Suemi Kamoi Kay ◽  
Rosana Herminia Scola
Keyword(s):  
Multiple Sclerosis ◽  
Human Leukocyte Antigen ◽  
Human Leukocyte ◽  
Hla Class I ◽  
Class I ◽  
Interferon Β ◽  
Leukocyte Antigen ◽  
Specific Subset ◽  
Hla Type ◽  
Disease Modifying

ABSTRACT Objective: To investigate the potential relationship between the human leukocyte antigen (HLA) type (class I and II) and the response to several disease-modifying therapies (DMTs) in patients with multiple sclerosis (MS). Methods: We analyzed clinical data of 87 patients with MS at the beginning and end of each type of DMT including the disease duration, Expanded Disability Status Scale and Multiple Sclerosis Severity Score (MSSS). Genotyping of HLA-DRB1, HLA-DPB1, HLA-DQB1, HLA-A, HLA-B and HLA-C alleles were identified using high-resolution techniques. Statistical correlation between the HLA type and response to DMTs was done using the initial and final MSSS. Results: Statistical relationships (p < 0.05) were found for only 15 of 245 alleles tested. There was a reduction in the MSSS for patients treated with corticosteroids (DRB1*15:01, DPB1*04:01, DQB1*02:01 and DQB1*03:01), azathioprine (DRB1*03:01, DPB1*04:01, DQB1*03:02, DQB1*06:02, HLA-C*07:02), interferon β-1a 22 mcg (DRB1*11:04, DQB1*03:01 and DQB1*03:02), interferon β-1a 30 mcg (DPB1*02:01, HLA-C*05:01) and interferon β-1b (DQB1*02:01). Conclusion: These findings suggest a few relationships between the HLA and response to DMTs in the disability for some types of HLA class I and II alleles in a specific subset of MS patients.

scholarly journals Human Leukocyte Antigen (HLA) class I and II datasets for sudanese

Data in Brief ◽  
2019 ◽  
Vol 24 ◽  
pp. 104027
Author(s):  
Ameer Mohamed Dafalla ◽  
Hisham Atan Edinur ◽  
Mohammed Abdelwahed ◽  
Almutaz Abbas Elemam ◽  
Amel Abdeen Ibrahim ◽  
...  
Keyword(s):  
Human Leukocyte Antigen ◽  
Human Leukocyte ◽  
Hla Class I ◽  
Class I ◽  
Leukocyte Antigen

scholarly journals Co-evolution of Human Leukocyte Antigen (HLA) Class I Ligands with Killer-Cell Immunoglobulin-Like Receptors (KIR) in a Genetically Diverse Population of Sub-Saharan Africans

PLoS Genetics ◽  
2013 ◽  
Vol 9 (10) ◽  
pp. e1003938 ◽  
Author(s):  
Paul J. Norman ◽  
Jill A. Hollenbach ◽  
Neda Nemat-Gorgani ◽  
Lisbeth A. Guethlein ◽  
Hugo G. Hilton ◽  
...  
Keyword(s):  
Human Leukocyte Antigen ◽  
Killer Cell ◽  
Human Leukocyte ◽  
Hla Class I ◽  
Class I ◽  
Diverse Population ◽  
Leukocyte Antigen ◽  
Sub Saharan

scholarly journals Immunogenetic Epidemiology of Dementia and Parkinson’s Disease in 14 Continental European Countries: Shared Human Leukocyte Antigen (HLA) Profiles

2021 ◽  
Vol 5 (2) ◽  
pp. 16-26
Author(s):  
Lisa M. James ◽  
Apostolos P. Georgopoulos
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Human Leukocyte Antigen ◽  
Human Leukocyte ◽  
Hla Class I ◽  
European Countries ◽  
Class I ◽  
Protective Mechanisms ◽  
Leukocyte Antigen ◽  
Epidemiology Of Dementia

Human leukocyte antigen (HLA), which is critically involved in immune response to foreign antigens and in autoimmunity, has been implicated in dementia and Parkinson’s disease. Here we report on the correlations between the population frequencies of 127 HLA Class I and II alleles and the population prevalence of dementia and Parkinson’s disease in 14 Continental Western European countries, extending previous work1,2. We used these correlations to construct and compare HLA profiles for each disease3. We found that (a) the HLA profiles of the two diseases were significantly correlated across both HLA Class I and Class II alleles, (b) negative (“protective”) HLA-disease correlations did not differ significantly for either HLA class, but (c) positive (“susceptibility”) HLA-disease correlations were significantly higher in dementia than in Parkinson’s disease for both HLA classes of alleles. These findings indicate that (a) dementia and Parkinson’s disease share immunogenetic HLA-related mechanisms, (b) HLA-related protective mechanisms (presumably against pathogens) do not differ between the two diseases, but (c) HLA-related susceptibility mechanisms (presumably underlying autoimmunity) are significantly stronger in dementia than in Parkinson’s disease.

scholarly journals ASOSIASI HUMAN LEUKOCYTE ANTIGEN (HLA) KARSINOMA NASOFARING (KNF)

2018 ◽  
Vol 15 (2) ◽  
pp. 52
Author(s):  
F.M. Judajana
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Human Leukocyte Antigen ◽  
B Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Human Leukocyte ◽  
Hla Class I ◽  
Genetic System ◽  
Class I ◽  
Leukocyte Antigen ◽  
Barr Virus

Nasopharyngeal Carcinoma (NPC) is one of the most frequent malignancy disease in Java and the incidence rate at several Hospitalsseems increasing yearly. Prevalence of NCP in Indonesian were 3.9 per 100.000 citizen each year. Eipsten-Barr Virus (EBV) is one of theetiological agents of Nasopharyngeal Carcinoma (NPC) and infected B lymphocyte that cause transformation of it to LymphoblastoidCell Line and expresses several antigens. One of them is known as Latent membrane Protein 2A (LMP2A). These antigens is the maintarget of Cytotoxic T lymphocyte (CTL) in immune system surveillance by recognizing an epitope Human Leukocyte Antigen (HLA)class I complexes which expressed on the target cell surface. Beside EBV, there are other factors that. Research of the HLA class I antigenis one of the immune genetic system that has the ability as genetic sensitivity to the disease. The research in NPC patients is not tobe done to show representative for of population in Indonesia especially in Java. The aim of the study was to know the associationbetween HLA class I profile and NPC patients in Java population and to isolate lymphocyte from peripheral blood 24 NPC patients formicrolymphocytotoxicity test with Terasaki Plate derived from UCLA-USA. The results is significantly associated to HLA – A 24 (RR 2.25),HLA A2 (RR 1.635) and HLA A11 (RR 1.065). Based on these HLA class 1 profile as an immune genetics marker on NPC is one of themost important target. In order to develop EBV vaccine in the future, this is necessary especially for Java Population in Indonesia.

scholarly journals The anti-tumour effect of CD8+ infiltration is associated with Human Leukocyte Antigen Class I expression and tumour proliferation in colorectal cancer

2020 ◽  
Author(s):  
Arfon G M T Powell ◽  
Colin Richards ◽  
Jonathan J Platt ◽  
Clare Orange ◽  
Lindsay Bennett ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Inflammatory Response ◽  
Human Leukocyte Antigen ◽  
Cancer Cell ◽  
Human Leukocyte ◽  
Hla Class I ◽  
Class I ◽  
Local Inflammatory Response ◽  
Leukocyte Antigen ◽  
Tumour Proliferation

AbstractPurposeThe host inflammatory response is an important determinant of cancer outcome, however, the factor/s that regulate this response remains unclear. We aimed to determine if Human Leukocyte Antigen (HLA) class I and tumour cell proliferation are associated with CD8+ infiltration and survival in patients undergoing potentially curative resection for colorectal cancer.MethodsHLA class I expression (W6/32 and B2-microglobulin) and tumour proliferation index (Ki67) were quantified using immunohistochemistry on tissue micro arrays (TMA). The local inflammatory response at the invasive margin was assessed using the Klintrup-Makinen (K-M) score and CD8+ infiltration was assessed at the invasive margin (mCD8+), stroma (sCD8+) and cancer cell nests (cCD8+).ResultsPreserved HLA class I expression was associated with lower Dukes’ stage (p=0.032), lower T stage (p=0.040) and higher cCD8+ (p=0.003). High Ki67 was associated with a good K-M score (p<0.001), higher mCD8+ (p=0.033), higher sCD8+ (p=0.025) and higher cCD8+ (p<0.001). On binary logistical regression analysis both preserved HLA class I expression (HR 1.99 95%CI (1.13–3.51),p=0.012) and high Ki67 (HR 2.63 95%CI (1.08–6.38),p=0.033) were independently associated with higher CD8+ infiltration within the cancer cell nests. On multivariate survival analysis, preserved HLA class I expression was associated with disease free (HR 0.47 95%CI (0.25–0.89),p=0.020) and cancer specific survival (HR 0.52 95%CI (0.28–0.97),p=0.038).ConclusionThis study suggests that a pronounced local inflammatory response is independently associated with both, HLA class I expression and tumour proliferation.

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