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

Ji, Wei; Niu, Ling; Peng, Wanyue; Zhang, Yongli; Cheng, Hao; Gao, Feng; Shi, Yi; Qi, Jianxun; Gao, George F.; Liu, William J.

doi:10.1016/j.molimm.2019.06.005

Cited by 6 publications

(4 citation statements)

References 27 publications

(31 reference statements)

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“…We observed salt bridge‐forming residues positioned over the viral epitopes in three of the five complexes, as well as continuous hydrogen bonding between epitopes and HLA chains maintained throughout the simulation in all complexes (Figure 1B,C). Mutations in salt bridge‐forming amino acids have been shown to weaken TCR recognition of MHC class I‐antigen complexes 19 . Also, the continuous formation of a set of hydrogen bonds between the MHC molecules and epitopes indicates an accommodating nature of the HLA chains to bind epitopes within the groove between the two helices 20 .…”

Section: Resultsmentioning

confidence: 66%

Immunoinformatics‐aided identification of T cell and B cell epitopes in the surface glycoprotein of 2019‐nCoV

Baruah

Bose

2020

Journal of Medical Virology

281

273

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The 2019 novel coronavirus (2019-nCoV) outbreak has caused a large number of deaths with thousands of confirmed cases worldwide, especially in East Asia.This study took an immunoinformatics approach to identify significant cytotoxic T lymphocyte (CTL) and B cell epitopes in the 2019-nCoV surface glycoprotein. Also, interactions between identified CTL epitopes and their corresponding major histocompatibility complex (MHC) class I supertype representatives prevalent in China were studied by molecular dynamics simulations. We identified five CTL epitopes, three sequential B cell epitopes and five discontinuous B cell epitopes in the viral surface glycoprotein. Also, during simulations, the CTL epitopes were observed to be binding MHC class I peptide-binding grooves via multiple contacts, with continuous hydrogen bonds and salt bridge anchors, indicating their potential in generating immune responses. Some of these identified epitopes can be potential candidates for the development of 2019-nCoV vaccines.

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Section: Resultsmentioning

confidence: 66%

Immunoinformatics‐aided identification of T cell and B cell epitopes in the surface glycoprotein of 2019‐nCoV

Baruah

Bose

2020

Journal of Medical Virology

281

273

View full text Add to dashboard Cite

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“…3A ; Figure S13D, Supplementary Material ). Comparative MD simulations of GLKEGIPAL and GVKEGIPAL peptides showed that while both formed similar hydrogen bonds, V2 was closer to the beta-floor sheet than L2, consistent with tighter binding in the B pocket and improved peptide stability ( Figures S13E and S13F, Supplementary Material ) ( 43 , 44 ). Furthermore, comparison of the relative movements of p66 residues indicated that N66 was more mobile with L2 but more stable with V2 present; by contrast, K66 made stable interactions with either L2 or V2 (Fig.…”

Section: Resultsmentioning

confidence: 76%

Charge-based interactions through peptide position 4 drive diversity of antigen presentation by human leukocyte antigen class I molecules

et al. 2022

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Human leukocyte antigen class I (HLA-I) molecules bind and present peptides at the cell surface to facilitate the induction of appropriate CD8 + T cell-mediated immune responses to pathogen- and self-derived proteins. The HLA-I peptide-binding cleft contains dominant anchor sites in the B and F pockets that interact primarily with amino acids at peptide position 2 and the C-terminus, respectively. Non-pocket peptide-HLA interactions also contribute to peptide binding and stability, but these secondary interactions are thought to be unique to individual HLA allotypes or to specific peptide antigens. Here we show that two conserved positively charged residues located near the top of peptide-binding cleft facilitate interactions with negatively charged residues at position 4 of presented peptides, which occur at elevated frequencies across most HLA-I allotypes. Loss of these interactions was shown to impair HLA-I/peptide binding and complex stability, as demonstrated by both in vitro and in silico experiments. Furthermore, mutation of these Arginine-65 (R65) and/or Lysine-66 (K66) residues in HLA-A*02:01 and A*24:02 significantly reduced HLA-I cell surface expression while also reducing the diversity of the presented peptide repertoire by up to five-fold. The impact of the R65 mutation demonstrates that non-pocket HLA-I/peptide interactions can constitute anchor motifs that exert an unexpectedly broad influence on HLA-I mediated antigen presentation. These findings provide fundamental insights into peptide antigen binding that could broadly inform epitope discovery in the context of viral vaccine development and cancer immunotherapy.

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“…Homologous epitopes from other coronaviruses have the potential to elicit cross T cell responses to SARS-CoV-2 infection, so we also summarized the structures of HLA complexes loaded with SARS-CoV-derived peptides (Table 1 and Fig. 2A) [60,[77][78][79][80][81]. Three peptides are based on the HLA-A*0201-restricted type, and there is one for each of the other HLA alleles, i.e., HLA-A*2402, HLA-B*1501, HLA-A*1101, and HLA-B*4001.…”

Section: Potential For Cross-t Cell Recognition Of Sars-cov-2 and Sar...mentioning

confidence: 99%

Seeing the T cell Immunity of SARS-CoV-2 and SARS-CoV: Believing the Epitope-Oriented Vaccines

Cui¹,

Wang²,

Tian³

et al. 2023

Int. J. Biol. Sci.

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The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at the end of 2019 stimulated vigorous research efforts in immunology and vaccinology. In addition to innate immune responses, both virus-specific humoral and cellular immune responses are of importance for viral clearance. T cell epitopes play a central role in T cell-based immune responses. Herein, we summarized the peptide/major histocompatibility complex (pMHC) structures of the SARS-CoV-2-derived T cell epitopes available in the Protein Data Bank (PDB) and proposed the challenge and opportunities for using of T cell epitopes in future vaccine development efforts. A total of 27 SARS-CoV-2 related pMHC structures and five complexes with T cell receptors were retrieved. The peptides are mainly distributed on spike (S), nucleocapsid (N), and ORF1ab proteins. Most peptides are conserved among variants of concerns (VOCs) for SARS-CoV-2, except for several mutated peptides located in the S protein. The structures of human leukocyte antigen (HLA) complexed with seven epitopes derived from SARS-CoV were also retrieved, which showed a potential cross T cell immunity with SARS-CoV-2. Structural studies of antigenic peptides from SARS-CoV-2 and SARS-CoV help to visualize the processes and the mechanisms of cross T cell immunity. T cell epitope-oriented vaccines are potential next-generation vaccines for SARS-CoV-2, which are worthy of further investigation.

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

Cited by 6 publications

References 27 publications

Immunoinformatics‐aided identification of T cell and B cell epitopes in the surface glycoprotein of 2019‐nCoV

Immunoinformatics‐aided identification of T cell and B cell epitopes in the surface glycoprotein of 2019‐nCoV

Charge-based interactions through peptide position 4 drive diversity of antigen presentation by human leukocyte antigen class I molecules

Seeing the T cell Immunity of SARS-CoV-2 and SARS-CoV: Believing the Epitope-Oriented Vaccines

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