scholarly journals A25 Impact of polymorphism in the hepatitis B surface gene on human leukocyte antigen (HLA) class II

2019 ◽  
Vol 5 (Supplement_1) ◽  
Author(s):  
W -T Choga ◽  
M Anderson ◽  
B -B Phinius ◽  
T Mbangiwa ◽  
T -G Bell ◽  
...  
Keyword(s):  
Hepatitis B ◽  
Human Leukocyte ◽  
Class Ii ◽  
Hla Class Ii ◽  
Antigenic Peptides ◽  
Immunological Responses ◽  
Chronic Hepatitis B Virus ◽  
Liver Cancers ◽  
Surface Gene ◽  
Genotype A

Abstract There is still no cure for chronic hepatitis B virus infection (CHBV), a major cause of liver cancers and related malignancies. Elucidating the role of CD4+ T-helper cells in activating immunological responses that clear antigenic peptides during primary HBV infection holds a potential strategy for developing potent vaccines. Since the strength of CD4+ T cell responses is dictated by binding of viral epitopes to class-II human leukocyte antigens (HLAs), we hypothesize that the quality of immunological responses in CHBV patients is influenced by host genetics and HBV genotypes. Here, ninety-two non-recombinant complete HBV surface-gene proteins (PreS1/S) from Botswana were sequenced (genotype A 44(47.8%); D 48(52.2%)) and 15-mer binding epitopes restricted to nine HLA-class II molecules (DRB5/1) were mapped in silico. The HLAs used have high population coverage in Botswana. The total predicted epitopes per HLA were 94-(genotype A) and 105-(genotype D) for PreS1, 42 (A and D) for PreS2, and 105 (A and D) for S. Epitope densities (binding peptides to total epitopes) were 3 per cent and 6 per cent (PreS1A&D), 4 per cent and 2 per cent (PreS2A&D), and 23 per cent and 22 per cent (S1A&D). SA&D proteins had most polytopes: CPGYRWMCLRRFII66-81, PGYRWMCLRRFIIF67-82, GYRWMCLRRFIIFL68-83, and YRWMCLRRFIIFLF69-84 binding to 5 (55.6%) HLAs (DRB1*0101/0701/1101/1501 and DRB5*0101) used. HLA-DRB*0101 bound the most epitopes, and the least were bound by HLA-DRB*0302/0701/0401 for both genotypes. PreS1D polytope: PAFRANTANPDWDFN32-46 binds to DRB1*0101/0401/1302 and PreS2 polytopes: TAFHQALQDPRVRG6-19 and AFHQALQDPRVRGL7-20 bind to DRB1*010/1501 alleles. Non-synonymous mutations impair peptide-HLA binding when assessed as combinations of > 2. The least active HLAs may be associated with CHBV and vice-versa for HBV clearance, thus the algorithm may be used to predict HBV prognosis for different haplotypes. The results favor the use of epitopes from S protein as broad genotype vaccine. This study highlights the need to explore further the mechanisms of PreS1 and its effect on the immune system.

scholarly journals In Silico Prediction of Human Leukocytes Antigen (HLA) Class II Binding Hepatitis B Virus (HBV) Peptides in Botswana

Viruses ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 731 ◽  
Author(s):  
Wonderful Tatenda Choga ◽  
Motswedi Anderson ◽  
Edward Zumbika ◽  
Bonolo B. Phinius ◽  
Tshepiso Mbangiwa ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
In Silico ◽  
Class Ii ◽  
Hla Class Ii ◽  
Hbv Infection ◽  
Diagnostic Kits ◽  
Immunological Responses ◽  
B Virus ◽  
Epitope Vaccines

Hepatitis B virus (HBV) is the primary cause of liver-related malignancies worldwide, and there is no effective cure for chronic HBV infection (CHB) currently. Strong immunological responses induced by T cells are associated with HBV clearance during acute infection; however, the repertoire of epitopes (epi) presented by major histocompatibility complexes (MHCs) to elicit these responses in various African populations is not well understood. In silico approaches were used to map and investigate 15-mers HBV peptides restricted to 9 HLA class II alleles with high population coverage in Botswana. Sequences from 44 HBV genotype A and 48 genotype D surface genes (PreS/S) from Botswana were used. Of the 1819 epi bindings predicted, 20.2% were strong binders (SB), and none of the putative epi bind to all the 9 alleles suggesting that multi-epitope, genotype-based, population-based vaccines will be more effective against HBV infections as opposed to previously proposed broad potency epitope-vaccines which were assumed to work for all alleles. In total, there were 297 unique epi predicted from the 3 proteins and amongst, S regions had the highest number of epi (n = 186). Epitope-densities (Depi) between genotypes A and D were similar. A number of mutations that hindered HLA-peptide binding were observed. We also identified antigenic and genotype-specific peptides with characteristics that are well suited for the development of sensitive diagnostic kits. This study identified candidate peptides that can be used for developing multi-epitope vaccines and highly sensitive diagnostic kits against HBV infection in an African population. Our results suggest that viral variability may hinder HBV peptide-MHC binding, required to initiate a cascade of immunological responses against infection.

scholarly journals Preliminary Identification of Human Leukocyte Antigen (HLA) CLASS II DRB1 Allelic Variants in Selected Filipino Cancer Patient Samples

2020 ◽  
Vol 54 (4) ◽  
Author(s):  
Jemicah Tristian P. Cobarrubias ◽  
Ciara Christianne Y. Lim ◽  
Ma. Teresa A. Barzaga ◽  
Francisco M. Heralde III
Keyword(s):  
Cancer Patient ◽  
Human Leukocyte Antigen ◽  
Cancer Patients ◽  
Human Leukocyte ◽  
Class Ii ◽  
Hla Class Ii ◽  
Antigenic Peptides ◽  
Rt Pcr ◽  
Allelic Variants ◽  
Leukocyte Antigen

Objective. The Human Leukocyte Antigen (HLA) Class II is the major histocompatibility complex surface glycoproteins of humans responsible for presenting exogenous antigenic peptides which help direct specificity of immune response. In immune-cell therapy, the HLA allelic variants are of particular importance as they determine the successful activation of target cells that results to a desired therapeutic response. However, HLA Class II exhibits high polymorphism and has variable distribution in population, constituting these so-called allelic variants. Specifically, the HLA Class II DRB1 is considered the predominant locus among Filipinos. This research aimed to identify the presence of HLA Class II DRB1 allelic variants in the stem cell samples of ten (10) Filipino cancer patients by reverse transcription polymerase chain reaction (RT-PCR) amplification.Method. This study employed a PCR-based HLA Class II typing to identify the HLA Class II DRB1 allelic variant in Filipino cancer patients. Design of forward and reverse primers for HLA Class II DRB1, optimization of PCR conditions for amplifying HLA Class II DRB1, and identification of HLA Class II DRB1 allelic variants from samples by sequencing and database comparison were conducted.Results. PCR optimization showed that optimum annealing temperature for HLA DRB1 was 58.8°C with 1 mM MgCl2. PCR amplification of HLA DRB1 from ten anonymized cancer patient samples and DNA sequencing revealed that Patients 1, 2, 5, 8, 9, and 10 harbor HLA DRB1 allelic variants, particularly, the HLA DRB1*04:06:01, HLA DRB1*12:01:01, HLA DRB1*0813, HLA DRB1*04:05:01, HLA DRB1*09:01:02, and HLA DRB1*16:02:01, allelic variants, respectively.Conclusion. Using the designed primers and optimized RT-PCR protocol, HLA information derived from six out of ten patient samples can be used for further applications in developing personalized or generic antigenic peptides such as dendritic cell cancer vaccine.

scholarly journals Binding of Human Thyrotropin Receptor Peptides to a Graves’ Disease-Predisposing Human Leukocyte Antigen Class II Molecule

2000 ◽  
Vol 85 (3) ◽  
pp. 1176-1179 ◽  
Author(s):  
Yoshikuni Sawai ◽  
Leslie J. DeGroot
Keyword(s):  
Human Leukocyte Antigen ◽  
Human Leukocyte ◽  
Class Ii ◽  
Hla Class Ii ◽  
Graves Disease ◽  
T Cell Repertoire ◽  
Thyrotropin Receptor ◽  
Cell Repertoire ◽  
Peptide Epitopes ◽  
Leukocyte Antigen

Abstract Abstract There are many reports that Graves’ disease (GD) is associated with certain human leukocyte antigen (HLA) molecules, in particular DR3. Here we examined the characteristics of binding of human TSH receptor (TSHR) peptides to this disease-associated HLA class II molecule. DR3 molecules bind TSHR immuonodominant peptide epitopes with intermediate affinity. On the contrary, DR3 binds nonimmunogenic peptides either with poor affinity or not at all, with one exceptional peptide that has extremely high affinity. These results suggest that susceptibility to GD associated with inheritance of a specific HLA class II gene is due to the influence of the HLA molecule-TSHR peptide complex on the T cell repertoire.

scholarly journals Shared HLA Class II in Six Autoimmune Diseases in Latin America: A Meta-Analysis

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Paola Cruz-Tapias ◽  
Oscar M. Pérez-Fernández ◽  
Adriana Rojas-Villarraga ◽  
Alberto Rodríguez-Rodríguez ◽  
María-Teresa Arango ◽  
...  
Keyword(s):  
Risk Factor ◽  
Autoimmune Diseases ◽  
Lupus Erythematosus ◽  
Meta Analysis ◽  
Human Leukocyte ◽  
Class Ii ◽  
Hla Class Ii ◽  
Genetic Characteristics ◽  
Latin Americans ◽  
Leukocyte Antigen

The prevalence and genetic susceptibility of autoimmune diseases (ADs) may vary depending on latitudinal gradient and ethnicity. The aims of this study were to identify common human leukocyte antigen (HLA) class II alleles that contribute to susceptibility to six ADs in Latin Americans through a meta-analysis and to review additional clinical, immunological, and genetic characteristics of those ADs sharing HLA alleles. DRB1∗03:01 (OR: 4.04; 95%CI: 1.41–11.53) was found to be a risk factor for systemic lupus erythematosus (SLE), Sjögren's syndrome (SS), and type 1 diabetes mellitus (T1D). DRB1∗04:05 (OR: 4.64; 95%CI: 2.14–10.05) influences autoimmune hepatitis (AIH), rheumatoid arthritis (RA), and T1D; DRB1∗04:01 (OR: 3.86; 95%CI: 2.32–6.42) is a susceptibility factor for RA and T1D. Opposite associations were found between multiple sclerosis (MS) and T1D. DQB1∗06:02 and DRB1∗15 alleles were risk factors for MS but protective factors for T1D. Likewise, DQB1∗06:03 allele was a risk factor for AIH but a protective one for T1D. Several common autoantibodies and clinical associations as well as additional shared genes have been reported in these ADs, which are reviewed herein. These results indicate that in Latin Americans ADs share major loci and immune characteristics.

scholarly journals HLA Class II-DRB,-DQA and –DQB Genotypes in Peripheral Blood Shows Shifts During the Course of Sepsis

2019 ◽  
Vol 73 (1) ◽  
pp. 10-16
Author(s):  
Linda Bāra ◽  
Jeļena Eglīte ◽  
Pēteris Ošs ◽  
Vinita Cauce ◽  
Vilnis Lietuvietis ◽  
...  
Keyword(s):  
Human Leukocyte ◽  
Class Ii ◽  
Hla Class Ii ◽  
University Hospital ◽  
Control Group ◽  
Hla Dr ◽  
Group Data ◽  
Threatening Condition ◽  
Life Threatening ◽  
Genetically Determined

Abstract Undeniably, sepsis is still a profoundly damaging and life-threatening condition for many individuals. With multiple changes in sepsis patients it is difficult to precisely classify an individual’s response in sepsis as proinflammatory or immunosuppressed. The aim of this study was to investigate genetically determined predisposition to developed sepsis by analysis of distribution of human leukocyte antigen (HLA) class II genes. Samples from patients with sepsis were collected at Pauls Stradiņš Clinical University Hospital, Latvia, in an intensive care unit between October 2016 and May 2017. The study group included 62 patients with sepsis, who were genotyped for HLA-DR; DQ using real time polymerase chain reaction – sequence specific primer (RT PCR-SSP). As a control group, data of 100 individuals were taken from the genetic bank of RSU Joint Laboratory of Clinical Immunology and Immunogenetics. The summarised results showed that the frequency of alleles DRB1*04:01 (OR = 5.54; 95% CI = 1.88–16.29); DRB1*07:01 (OR = 19.03; 95% CI = 2/37–152.82); DQA1*05:01 (OR = 14.17; 95% CI = 5.67–35.4); and DQB1*02:01 (OR = 50.00; 95% CI = 2.90–861.81) were significantly increased in patients with sepsis compared to the control group patients. The frequency of DRB1*16:01 (OR = 0.17, 95% CI = 0.04–0.59); DRB1*17:01 (OR = 0.04; 95% CI = 0.00–0.69); DQA1*01:01 (OR = 0.04; 95% CI = 0.00–0.31); DQA1*01:02 (OR = 0.03; 95% CI = 0.00–0.23); DQB1*02:02 (OR = 0.12; 95% CI = 0.03–0.42) alleles was lower in sepsis patients than in control subjects. The most frequent HLA-DRB1/DQA1/DQB1 haplotypes that was significantly increased in patients with sepsis were: DRB1*01:01/DQA1*05:01/DQB1*03:01 (OR = 12.6; 95% CI = 1.51–105.0; p < 0.003). Sepsis patients with pneumonia and alleles and DRB1 04:01; 07:01, DQB1 02:01 had the highest mortality rate. Undoubtedly, our preliminary data showed that development of sepsis can be associated with alleles and haplotypes of HLA class II genes. For more precise conclusion the research should be continued to include a larger patient group.

scholarly journals Identification of MAGE-3 Epitopes Presented by HLA-DR Molecules to CD4+ T Lymphocytes

1999 ◽  
Vol 189 (5) ◽  
pp. 767-778 ◽  
Author(s):  
Pascal Chaux ◽  
Valérie Vantomme ◽  
Vincent Stroobant ◽  
Kris Thielemans ◽  
Jurgen Corthals ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Tumor Antigens ◽  
Class Ii ◽  
Hla Class Ii ◽  
Antigenic Peptides ◽  
Recombinant Viruses ◽  
Mhc Molecules ◽  
Hla Dr ◽  
Cell Clones ◽  
Hla Class Ii Molecules

MAGE-type genes are expressed by many tumors of different histological types and not by normal cells, except for male germline cells, which do not express major histocompatibility complex (MHC) molecules. Therefore, the antigens encoded by MAGE-type genes are strictly tumor specific and common to many tumors. We describe here the identification of the first MAGE-encoded epitopes presented by histocompatibility leukocyte antigen (HLA) class II molecules to CD4+ T lymphocytes. Monocyte-derived dendritic cells were loaded with a MAGE-3 recombinant protein and used to stimulate autologous CD4+ T cells. We isolated CD4+ T cell clones that recognized two different MAGE-3 epitopes, MAGE-3114–127 and MAGE-3121–134, both presented by the HLA-DR13 molecule, which is expressed in 20% of Caucasians. The second epitope is also encoded by MAGE-1, -2, and -6. Our procedure should be applicable to other proteins for the identification of new tumor-specific antigens presented by HLA class II molecules. The knowledge of such antigens will be useful for evaluation of the immune response of cancer patients immunized with proteins or with recombinant viruses carrying entire genes coding for tumor antigens. The use of antigenic peptides presented by class II in addition to peptides presented by class I may also improve the efficacy of therapeutic antitumor vaccination.

scholarly journals Susceptible and Protective Human Leukocyte Antigen Class II Alleles and Haplotypes in Bahraini Type 2 (Non-Insulin-Dependent) Diabetes Mellitus Patients

2005 ◽  
Vol 12 (1) ◽  
pp. 213-217 ◽  
Author(s):  
Ayesha A. Motala ◽  
Marc Busson ◽  
Einas M. Al-Harbi ◽  
Manal A. A. Khuzam ◽  
Emtiaz M. D. Al-Omari ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Type 1 Diabetes ◽  
Human Leukocyte Antigen ◽  
Human Leukocyte ◽  
Class Ii ◽  
Hla Class Ii ◽  
Leukocyte Antigen ◽  
Insulin Dependent

ABSTRACT Whereas the genetic risk for type 1 diabetes is linked to human leukocyte antigen (HLA) class II genes, the HLA association in type 2 (non-insulin-dependent) diabetes is less clear. The association between HLA class II genotypes and type 2 diabetes was examined in adult Bahrainis, an Arab population with a high prevalence of type 2 diabetes. HLA-DRB1* and -DQB1* genotyping of 86 unrelated type 2 diabetes patients (age, 51.6 ± 8.2 years; mean duration of diabetes, 7.7 ± 7.1 years) who had a strong family history of diabetes (52 of 72 versus 0 of 89 for controls, P < 0.001) and 89 healthy subjects was done by PCR-sequence-specific priming. DRB1*040101 (0.1221 versus 0.0562, P = 0.019) and DRB1*070101 (0.2151 versus 0.0843, P < 0.001) were positively associated, while DRB1*110101 (0.0698 versus 0.1461, P = 0.014) and DRB1*160101 (0.0640 versus 0.1236, P = 0.038) were negatively associated with type 2 diabetes. DRB1*040101-DQB1*0302 (0.069 versus 0.0007; P = 0.004), DRB1*070101-DQB1*0201 (0.178 versus 0.0761, P = 0.007), DRB1*070101-DQB1*050101 (0.125 versus 0.0310, P = 0.002), and DRB1*150101-DQB1*060101 (0.0756 versus 0.0281, P = 0.008) were more prevalent among patients, while DRB1*160101-DQB1*050101 (0.0702 versus 0.0349, P = 0.05) was more prevalent among controls, conferring disease susceptibility or protection, respectively. In Bahrainis with type 2 diabetes, there is a significant association with select HLA class II genotypes, which were distinct from those in type 1 diabetes.

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