Immunoprevalence and Immunodominance of HLA-Cw∗0801-Restricted T Cell Response Targeting the Hepatitis B Virus Envelope Transmembrane Region

Tan, Anthony T.; Sodsai, Pimpayao; Chia, Adeline; Moreau, E; Chng, Melissa Hui Yen; Tham, Christine Y.L.; Ho, Zi Zong; Banu, Nasirah; Hirankarn, Nattiya; Bertoletti, Antonio

doi:10.1128/jvi.02600-13

Cited by 14 publications

(13 citation statements)

References 17 publications

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“…6,7 The results in our study confirm that differences from the prototype epitope sequence (FLPSDFFPSV) were significantly enriched in HLA-A*02-positive individuals consistent with immune selection pressure in the presence of HLA-A*02. Interestingly, the frequency of sequence polymorphisms in the epitope was higher in genotype A compared to genotype D. This may reflect different functional constraints on the epitope region in different genotypes; however, it may also be the consequence of different frequencies of HLA-A*02 or different HLA-A*02 subtype distribution in patients infected with genotype A versus genotype D. It was previously reported that the epitope FLPSDFFPSV [18][19][20][21][22][23][24][25][26][27] is immunogenic in HLA-A*02:01 but not in HLA-A*02:03. 17 Moreover, in HCV there is evidence that the adaptation process to CD8 T-cell selection pressure is influenced at the HLA subtype level.…”

Section: Discussionmentioning

confidence: 95%

“…The analysis was focused on the HBV core protein as prior studies suggested that hepatitis B core antigen-specific immune responses are associated with immune control of HBV infection. 3 Earlier studies demonstrated that sequence variation in the dominant HLA-A*02-restricted epitope in HBV (core [18][19][20][21][22][23][24][25][26][27] ) functionally impaired the CD8 T-cell immune response. 6,7 The results in our study confirm that differences from the prototype epitope sequence (FLPSDFFPSV) were significantly enriched in HLA-A*02-positive individuals consistent with immune selection pressure in the presence of HLA-A*02.…”

Section: Discussionmentioning

confidence: 99%

“…Our analysis was limited to HLA-A and HLA-B. Although immunodominant epitopes restricted by HLA-C alleles have been described in HBV, 22 we decided to exclude the HLA-C locus from the analysis in order to have sufficient power for the statistical evaluation. Similar studies performed in HCV and HIV showed that viral sequence polymorphisms were predominantly associated with HLA-A and HLA-B alleles and less frequent with HLA-C alleles.…”

Section: Class I Allele Distribution Between Genotype Aand Genotype Dmentioning

confidence: 99%

“…Frequency of sequence polymorphisms in the CD8 T-cell epitope HBV core[18][19][20][21][22][23][24][25][26][27] . (A) The relative frequency of differences from the consensus sequence for each position of the epitope is shown for isolates collected from HLA-A*02-positive and HLA-A*02-negative patients.…”

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confidence: 99%

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Adaptation of the hepatitis B virus core protein to CD8+ T‐cell selection pressure

et al. 2015

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Activation of hepatitis B virus (HBV)-specific CD8 T cells by therapeutic vaccination may promote sustained control of viral replication by clearance of covalently closed circular DNA from infected hepatocytes. However, little is known about the exact targets of the CD8 T-cell response and whether HBV reproducibly evades CD8 T-cell immune pressure by mutation. The aim of this study was to address if HBV reproducibly selects substitutions in CD8 T-cell epitopes that functionally act as immune escape mutations. The HBV core gene was amplified and sequenced from 148 patients with chronic HBV infection, and the human leukocyte antigen (HLA) class I genotype (A and B loci) was determined. Residues under selection pressure in the presence of particular HLA class I alleles were identified by a statistical approach utilizing the novel analysis package SeqFeatR. With this approach we identified nine residues in HBV core under selection pressure in the presence of 10 different HLA class I alleles. Additional immunological experiments confirmed that seven of the residues were located inside epitopes targeted by patients with chronic HBV infection carrying the relevant HLA class I allele. Consistent with viral escape, the selected substitutions reproducibly impaired recognition by HBV-specific CD8 T cells. Conclusion: Viral sequence analysis allows identification of HLA class I-restricted epitopes under reproducible selection pressure in HBV core; the possibility of viral escape from CD8 T-cell immune pressure needs attention in the context of therapeutic vaccination against HBV. (HEPATOLOGY 2015;62:47-56) D espite an effective vaccine against hepatitis B virus (HBV) being available, chronic infections associated with the risk of progressive liver disease are an enormous public health problem affecting more than 240 million people worldwide. Effective suppression of viral replication by inhibition of the viral polymerase with nucleos(t)ide analogues is possible, but in most cases long-term or even lifelong treatment is necessary to avoid recurrence of viral replication. In this setting the concept of therapeutic vaccination potentially is an attractive strategy to achieve viral clearance.

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Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

Section: Class I Allele Distribution Between Genotype Aand Genotype Dmentioning

confidence: 99%

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confidence: 99%

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Adaptation of the hepatitis B virus core protein to CD8+ T‐cell selection pressure

et al. 2015

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“…In addition, we also detected CTL responses in all HLA-C*08-positive individuals, suggesting that the immunoprevalence of HLA-C*08-restricted GILGFVFTL responses in the human population may be comparable to that of HLA-A*02-restricted responses. Interestingly, among HLA-C molecules, HLA-C*08:01 appears to have broad peptide binding capacity, as shown in reports of binding to hepatitis B virus (HBV) envelope residues 171 to 180 (36,37) and CMV pp65 residues 198 to 206 (12). Whether the CTLs recognizing an identical epitope presented by unrelated HLA allelic variants were derived from the same CTL clones, resulting in T cell cross-reactivity, remains to be elucidated.…”

Section: Discussionmentioning

confidence: 99%

The Immunodominant Influenza A Virus M1_58–66Cytotoxic T Lymphocyte Epitope Exhibits Degenerate Class I Major Histocompatibility Complex Restriction in Humans

Choo

Liu

Toh

et al. 2014

J Virol

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Cytotoxic T lymphocytes recognizing conserved peptide epitopes are crucial for protection against influenza A virus (IAV) infection. The CD8 T cell response against the M1 58 -66 (GILGFVFTL) matrix protein epitope is immunodominant when restricted by HLA-A*02, a major histocompatibility complex (MHC) molecule expressed by approximately half of the human population. Here we report that the GILGFVFTL peptide is restricted by multiple HLA-C*08 alleles as well. We observed that M1 58 -66 was able to elicit cytotoxic T lymphocyte (CTL) responses in both HLA-A*02-and HLA-C*08-positive individuals and that GILG FVFTL-specific CTLs in individuals expressing both restriction elements were distinct and not cross-reactive. The crystal structure of GILGFVFTL-HLA-C*08:01 was solved at 1.84 Å, and comparison with the known GILGFVFTL-HLA-A*02:01 structure revealed that the antigen bound both complexes in near-identical conformations, accommodated by binding pockets shaped from shared as well as unique residues. This discovery of degenerate peptide presentation by both HLA-A and HLA-C allelic variants eliciting unique CTL responses to IAV infection contributes fundamental knowledge with important implications for vaccine development strategies. IMPORTANCEThe presentation of influenza A virus peptides to elicit immunity is thought to be narrowly restricted, with a single peptide presented by a specific HLA molecule. In this study, we show that the same influenza A virus peptide can be more broadly presented by both HLA-A and HLA-C molecules. This discovery may help to explain the differences in immunity to influenza A virus between individuals and populations and may also aid in the design of vaccines.

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A novel T-cell epitope in the transmembrane region of the hepatitis B virus envelope protein responds upon dendritic cell expansion

Chen

Zhang

et al. 2018

Arch Virol

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Restoring antiviral immunity is a promising immunotherapeutic approach to the treatment of chronic hepatitis B virus (HBV) infection. Dendritic cells play a crucial role in triggering antiviral immunity. In this study, we identified immunodominant epitopes prevalent in CD8 + T cell responses. We characterized the hierarchy of HBV epitopes targeted by CD8 + T cells following autologous monocyte-derived dendritic cell (moDC) expansion in HBV-infected subjects with distinct disease stages: treatment-naïve (TN group, n = 168), treatment with complete virological response (TR group, n = 72), and resolved HBV infection (RS group, n = 28). T cell responses against 32 HBV epitopes were measured upon moDC expansion. Several subdominant epitopes that triggered HBV-specific CD8 + T cell responses were identified. These epitopes’ responses varied in individuals with different disease stages. Moreover, the most immunodominant and immunoprevalent epitope included the envelope residues 256-270 (Env 256-270 ), corresponding to amino acid residues 93-107 in the small HBV surface protein (SHBs) across three patient groups. The frequency of Env 256-270 -specific interferon-γ-producing T cells was the highest in the RS group and the lowest in the TN group. In addition, individuals with HLA-A*02:03/02:06/02:07 were capable of responding to Env 256-270 . Env 256-270 -specific CD8 + T cells tolerated amino acid variations within the epitope detected in HBV genotypes B and C. This suggests that Env 256-270 in SHBs is crucial in HBV-specific T cell immunity following autologous moDC expansion. It might be a potential target epitope for dendritic-cell-based immunotherapy for CHB patients with complete viral suppression by long-term NAs treatment. Electronic supplementary material The online version of this article (10.1007/s00705-018-4095-0) contains supplementary material, which is available to authorized users.

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Immunoprevalence and Immunodominance of HLA-Cw∗0801-Restricted T Cell Response Targeting the Hepatitis B Virus Envelope Transmembrane Region

Cited by 14 publications

References 17 publications

Adaptation of the hepatitis B virus core protein to CD8+ T‐cell selection pressure

Adaptation of the hepatitis B virus core protein to CD8+ T‐cell selection pressure

The Immunodominant Influenza A Virus M1_58–66Cytotoxic T Lymphocyte Epitope Exhibits Degenerate Class I Major Histocompatibility Complex Restriction in Humans

A novel T-cell epitope in the transmembrane region of the hepatitis B virus envelope protein responds upon dendritic cell expansion

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Immunoprevalence and Immunodominance of HLA-Cw∗0801-Restricted T Cell Response Targeting the Hepatitis B Virus Envelope Transmembrane Region

Cited by 14 publications

References 17 publications

Adaptation of the hepatitis B virus core protein to CD8+ T‐cell selection pressure

Adaptation of the hepatitis B virus core protein to CD8+ T‐cell selection pressure

The Immunodominant Influenza A Virus M158–66Cytotoxic T Lymphocyte Epitope Exhibits Degenerate Class I Major Histocompatibility Complex Restriction in Humans

A novel T-cell epitope in the transmembrane region of the hepatitis B virus envelope protein responds upon dendritic cell expansion

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The Immunodominant Influenza A Virus M1_58–66Cytotoxic T Lymphocyte Epitope Exhibits Degenerate Class I Major Histocompatibility Complex Restriction in Humans