CpG oligodeoxynucleotides discriminately enhance binding capacity of human naïve B cells to Hepatitis B virus epitopes

2012 ◽  
Vol 58 (6) ◽  
pp. 752-759 ◽  
Author(s):  
Jian-ying Bai ◽  
Yong-tao Yang ◽  
Rong Zhu ◽  
Yi-qin Wang ◽  
Yin Tian ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
B Cells ◽  
Hepatitis B ◽  
Binding Capacity ◽  
Class Ii ◽  
Class I ◽  
Cpg Odn ◽  
Cpg Oligodeoxynucleotides ◽  
Class Ii Mhc ◽  
B Virus

CpG oligodeoxynucleotides (CpG ODN) have the potential to enhance the antigen-presenting cells function of human naïve B cells. In this study, we aim to define the effect of CpG ODNs on the binding capacity of human naïve B cells for different Hepatitis B virus (HBV) epitopes. Three HLA-A2 restricted epitopes were selected to incubate with CpG ODN-primed human naïve B cells. Binding capacity for each epitope and expression of CD80, CD86, class I major histocompatibility complex (MHC), and class II MHC of naïve B cells was tested, respectively, by flow cytometry. CpG ODNs, especially ODN 2216, enhanced the binding capacity of human naïve B cells for HBV epitopes (p < 0.01), and induced markedly higher expression of CD80, CD86, class I MHC, and class II MHC. The binding capacity of CpG-treated naive B cells for each epitope was significantly different. In all the 3 subjects, CpG ODN 2216-primed naïve B cells showed the highest binding ability for Env172–180 compared with the other epitopes with a high expression of co-stimulatory and MHC molecules. CpG ODN showed the potential to selectively enhance the binding capacity of human naïve B cells for HBV epitopes. These results suggest new strategies for development of vaccine design.

scholarly journals Comprehensive Analysis of Class I and Class II HLA Antigens and Chronic Hepatitis B Virus Infection

2003 ◽  
Vol 77 (22) ◽  
pp. 12083-12087 ◽  
Author(s):  
Chloe L. Thio ◽  
David L. Thomas ◽  
Peter Karacki ◽  
Xiaojiang Gao ◽  
Darlene Marti ◽  
...  
Keyword(s):  
Immune Response ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Viral Persistence ◽  
Class Ii ◽  
Viral Clearance ◽  
Hbv Infection ◽  
Class I ◽  
Chronic Hepatitis B Virus ◽  
B Virus

ABSTRACT Following an acute hepatitis B virus (HBV) infection, clearance or persistence is determined in part by the vigor and breadth of the host immune response. Since the human leukocyte antigen system (HLA) is an integral component of the immune response, we hypothesized that the highly polymorphic HLA genes are key determinants of viral clearance. HLA class I and II genes were molecularly typed in 194 Caucasian individuals with viral persistence and 342 matched controls who had cleared the virus. A single class I allele, A*0301 (odds ratio [OR], 0.47; 95% confidence interval [CI], 0.30 to 0.72; P = 0.0005) was associated with viral clearance. The class II allele DRB1*1302 was also associated with clearance (OR, 0.42; 95% CI, 0.19 to 0.93; P = 0.03), but its significance decreased in a multivariate model that included other alleles associated with disease outcome as covariates. B*08 was associated with viral persistence both independently (OR, 1.59; 95% CI, 1.04 to 2.43; P = 0.03) and as part of the conserved Caucasian haplotype A*01-B*08-DRB1*03. The B*44-Cw*1601 (OR, 2.23; 95% CI, 1.13 to 4.42; P = 0.02) and B*44-Cw*0501 (OR, 1.99; 95% CI, 1.22 to 3.24; P = 0.006) haplotypes were also associated with viral persistence. Interestingly, both the B*08 haplotype and DR7, which forms a haplotype with B*44-Cw*1601, have been associated with nonresponse to the HBV vaccine. The associations with class I alleles are consistent with a previously implicated role for CD8-mediated cytolytic-T-cell response in determining the outcome of an acute HBV infection.

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 Hepatitis B virus‐induced hyperactivation of B cells in chronic hepatitis B patients via TLR4

2020 ◽  
Vol 24 (11) ◽  
pp. 6096-6106
Author(s):  
Yang Li ◽  
Shengxia Yin ◽  
Yuxin Chen ◽  
Quan Zhang ◽  
Rui Huang ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis B Virus ◽  
B Cells ◽  
Hepatitis B ◽  
Chronic Hepatitis B ◽  
B Virus

Enhanced expression of HLA class I by inhibited replication of hepatitis B virus

1992 ◽  
Vol 14 (2-3) ◽  
pp. 232-236 ◽  
Author(s):  
Tetsuo Takehara ◽  
Norio Hayashi ◽  
Kazuhiro Katayama ◽  
Keiji Ueda ◽  
Takahiro Towata ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Hla Class I ◽  
Class I ◽  
B Virus ◽  
Enhanced Expression

scholarly journals Molecular Basis for the Interaction of the Hepatitis B Virus Core Antigen with the Surface Immunoglobulin Receptor on Naive B Cells

2001 ◽  
Vol 75 (14) ◽  
pp. 6367-6374 ◽  
Author(s):  
Una Lazdina ◽  
Tinghua Cao ◽  
Juris Steinbergs ◽  
Mats Alheim ◽  
Paul Pumpens ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
B Cells ◽  
Hepatitis B ◽  
Light Chain ◽  
Molecular Basis ◽  
Cell Surface Receptor ◽  
Core Antigen ◽  
Binding Motif ◽  
Linear Motif ◽  
B Virus

ABSTRACT The nucleocapsid of the hepatitis B virus (HBV) is composed of 180 to 240 copies of the HBV core (HBc) protein. HBc antigen (HBcAg) capsids are extremely immunogenic and can activate naive B cells by cross-linking their surface receptors. The molecular basis for the interaction between HBcAg and naive B cells is not known. The functionality of this activation was evidenced in that low concentrations of HBcAg, but not the nonparticulate homologue HBV envelope antigen (HBeAg), could prime naive B cells to produce anti-HBc in vitro with splenocytes from HBcAg- and HBeAg-specific T-cell receptor transgenic mice. The frequency of these HBcAg-binding B cells was estimated by both hybridoma techniques and flow cytometry (B7-2 induction and direct HBcAg binding) to be approximately 4 to 8% of the B cells in a naive spleen. Cloning and sequence analysis of the immunoglobulin heavy- and light-chain variable (VH and VL) domains of seven primary HBcAg-binding hybridomas revealed that six (86%) were related to the murine and human VH1 germ line gene families and one was related to the murine VH3 family. By using synthetic peptides spanning three VH1 sequences, one VH3 sequence, and one VLκV sequence, a linear motif in the framework region 1 (FR1)complementarity-determining region 1 (CDR1) junction of the VH1 sequence was identified that bound HBcAg. Interestingly, the HBcAg-binding motif was present in the VL domain of the HBcAg-binding VH3-encoded antibody. Finally, two monoclonal antibodies containing linear HBcAg-binding motifs blocked HBcAg presentation by purified naive B cells to purified HBcAg-primed CD4+ T cells. Thus, the ability of HBcAg to bind and activate a high frequency of naive B cells seems to be mediated through a linear motif present in the FR1-CDR1 junction of the heavy or light chain of the B-cell surface receptor.

A higher frequency of IL-10-producing B cells in Hepatitis B virus-associated membranous nephropathy

2016 ◽  
Vol 43 (4) ◽  
pp. 417-427 ◽  
Author(s):  
Yong Liu ◽  
Haifeng Wang ◽  
Xintong Hu ◽  
Zhihui Qu ◽  
Huimao Zhang ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
B Cells ◽  
Hepatitis B ◽  
Membranous Nephropathy ◽  
B Virus
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