Engineering T Cells Specific for a Dominant Severe Acute Respiratory Syndrome Coronavirus CD8 T Cell Epitope

Oh, Hsueh-Ling Janice; Chia, Adeline; Chang, Cynthia Xin Lei; Leong, Hoe Nam; Ling, Khoon Lin; Grotenbreg, Gijsbert M.; Gehring, Adam J.; Tan, Yee‐Joo; Bertoletti, Antonio

doi:10.1128/jvi.05039-11

Cited by 88 publications

(96 citation statements)

References 32 publications

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“…Recovered SARS individuals (6 y postinfection) were diagnosed with SARS based on clinical examination during the period from March to May 2003, according to the World Health Organization's definition of SARS (13). The diagnosis was further confirmed by serological detection of SARS-CoV-specific Abs by ELISA and/or RT-PCR for SARS-CoV mRNA, as described previously (14).…”

Section: Patient Samplesmentioning

confidence: 99%

Defining CD8+ T Cell Determinants during Human Viral Infection in Populations of Asian Ethnicity

Rivino

Tan

Chia

et al. 2013

The Journal of Immunology

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The identification of virus-specific CD8+ T cell determinants is a fundamental requirement for our understanding of viral disease pathogenesis. T cell epitope mapping strategies increasingly rely on algorithms that predict the binding of peptides to MHC molecules. There is, however, little information on the reliability of predictive algorithms in the context of human populations, in particular, for those expressing HLA class I molecules for which there are limited experimental data available. In this study, we evaluate the ability of NetMHCpan to predict antiviral CD8+ T cell epitopes that we identified with a traditional approach in patients of Asian ethnicity infected with Dengue virus, hepatitis B virus, or severe acute respiratory syndrome coronavirus. We experimentally demonstrate that the predictive power of algorithms defining peptide–MHC interaction directly correlates with the amount of training data on which the predictive algorithm has been constructed. These results highlight the limited applicability of the NetMHCpan algorithm for populations expressing HLA molecules for which there are little or no experimental binding data, such as those of Asian ethnicity.

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Section: Patient Samplesmentioning

confidence: 99%

Defining CD8+ T Cell Determinants during Human Viral Infection in Populations of Asian Ethnicity

Rivino

Tan

Chia

et al. 2013

The Journal of Immunology

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“…In humans, decreased T cell numbers (lymphopenia) correlated with severe disease, indicating the critical role of T cell-mediated immune response in disease development [11,12]. While SARS-specific antibody level in SARS-recovered individuals is undetectable at 6 years post-infection, SARS-specific memory T cells persisted up to 6 years following recovery [13]. The long-term persistence of memory T cell immunity could be important in protection against SARS-CoV re-infection.…”

Section: Introductionmentioning

confidence: 99%

Memory T cell responses targeting the SARS coronavirus persist up to 11 years post-infection

Chia

Tan

et al. 2016

Vaccine

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Severe acute respiratory syndrome (SARS) is a highly contagious infectious disease which first emerged in late 2002, caused by a then novel human coronavirus, SARS coronavirus (SARS-CoV). The virus is believed to have originated from bats and transmitted to human through intermediate animals such as civet cats. The re-emergence of SARS-CoV remains a valid concern due to the continual persistence of zoonotic SARS-CoVs and SARS-like CoVs (SL-CoVs) in bat reservoirs. In this study, the screening for the presence of SARS-specific T cells in a cohort of three SARS-recovered individuals at 9 and 11 years post-infection was carried out, and all memory T cell responses detected target the SARS-CoV structural proteins. Two CD8(+) T cell responses targeting the SARS-CoV membrane (M) and nucleocapsid (N) proteins were characterized by determining their HLA restriction and minimal T cell epitope regions. Furthermore, these responses were found to persist up to 11 years post-infection. An absence of cross-reactivity of these CD8(+) T cell responses against the newly-emerged Middle East respiratory syndrome coronavirus (MERS-CoV) was also demonstrated. The knowledge of the persistence of SARS-specific celullar immunity targeting the viral structural proteins in SARS-recovered individuals is important in the design and development of SARS vaccines, which are currently unavailable.

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“…The human HBV HBc protein-derived peptide HBc87-95 (SYVNT-NMGL) (Li et al, 2005) and SARS-CoV N protein-derived peptide N216-225 (GETALALLLL) (Oh et al, 2011) were synthesized with 95% purity by reverse-phase high performance liquid chromatography (SciLight Biotechnology, Beijing, China). The peptides were stored at −80°C as freeze-dried powders and were dissolved in dimethyl sulfoxide before use.…”

Section: Peptide Synthesis and Preparation Of Expression Constructsmentioning

confidence: 99%

“…Herein, by determining the crystal structures of human MHC I HLA-B*4001 complexed with a severe acute respiratory syndrome coronavirus (SARS-CoV) nucleocapsid (N)-derived T-cell epitope (Oh et al, 2011) and mouse MHC I H-2K d bound to an immunodominant T-cell epitope from human hepatitis B virus (HBV) core antigen (HBc) (Li et al, 2005), we clearly demonstrated the molecular features of MHC I molecules with two different salt bridges formed by the residues pairs Arg62-Glu163 and Arg66-Glu163, respectively. We further investigated the impacts of the salt bridges on peptide binding and T-cell recognition by constructing a series of MHC I mutants in vitro and in vivo.…”

Section: Introductionmentioning

confidence: 99%

Salt bridge-forming residues positioned over viral peptides presented by MHC class I impacts T-cell recognition in a binding-dependent manner

Niu

Peng

et al. 2019

Molecular Immunology

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A B S T R A C TThe viral peptides presentation by major histocompatibility complex class I (MHC I) molecules play a pivotal role in T-cell recognition and the subsequent virus clearance. This process is delicately adjusted by the variant residues of MHC I, especially the residues in the peptide binding groove (PBG). In a series of MHC I molecules, a salt bridge is formed above the N-terminus of the peptides. However, the potential impact of the salt bridge on peptide binding and T-cell receptor (TCR) recognition of MHC I, as well as the corresponding molecular basis, are still largely unknown. Herein, we determined the structures of HLA-B*4001 and H-2K d in which two different types of salt bridges (Arg62-Glu163 or Arg66-Glu163) across the PBG were observed. Although the two salt bridges led to different conformation shifts of both the MHC I α helix and the peptides, binding of the peptides with the salt bridge residues was relatively conserved. Furthermore, through a series of in vitro and in vivo investigations, we found that MHC I mutations that disrupt the salt bridge alleviate peptide binding and can weaken the TCR recognition of MHC I-peptide complexes. Our study may provide key references for understanding MHC I-restricted peptide recognition by T-cells.

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Engineering T Cells Specific for a Dominant Severe Acute Respiratory Syndrome Coronavirus CD8 T Cell Epitope

Cited by 88 publications

References 32 publications

Defining CD8+ T Cell Determinants during Human Viral Infection in Populations of Asian Ethnicity

Defining CD8+ T Cell Determinants during Human Viral Infection in Populations of Asian Ethnicity

Memory T cell responses targeting the SARS coronavirus persist up to 11 years post-infection

Salt bridge-forming residues positioned over viral peptides presented by MHC class I impacts T-cell recognition in a binding-dependent manner

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