Advances in T-Cell Epitope Engineering

Pentier, Johanne; Sewell, Andrew K.; Miles, John J.

doi:10.3389/fimmu.2013.00133

Cited by 11 publications

(11 citation statements)

References 46 publications

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“…Indeed, only now are we beginning to understand the pathological consequences of 'clonotype choice', which can determine host outcome in the face of pathogen challenge 33 , 34 , 35 , 36 . Ultimately, the ability to target and amplify 'ideal' precursors from the naive pool, possibly through the use of TCR‐optimized peptides to mobilize specific clonotypes, 37 , 38 , 39 could be a potent advance for biomedicine.…”

Section: Discussionmentioning

confidence: 99%

Naive CD8⁺ T‐cell precursors display structured TCR repertoires and composite antigen‐driven selection dynamics

et al. 2015

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Basic parameters of the naive antigen (Ag)-specific T-cell repertoire in humans remain poorly defined. Systematic characterization of this ‘ground state' immunity in comparison with memory will allow a better understanding of clonal selection during immune challenge. Here, we used high-definition cell isolation from umbilical cord blood samples to establish the baseline frequency, phenotype and T-cell antigen receptor (TCR) repertoire of CD8+ T-cell precursor populations specific for a range of viral and self-derived Ags. Across the board, these precursor populations were phenotypically naive and occurred with hierarchical frequencies clustered by Ag specificity. The corresponding patterns of TCR architecture were highly ordered and displayed partial overlap with adult memory, indicating biased structuring of the T-cell repertoire during Ag-driven selection. Collectively, these results provide new insights into the complex nature and dynamics of the naive T-cell compartment.

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Section: Discussionmentioning

confidence: 99%

Naive CD8⁺ T‐cell precursors display structured TCR repertoires and composite antigen‐driven selection dynamics

et al. 2015

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“…In this particular setting, however, the retroinverted D peptide was not immunogenic ( Supplemental Figure 1A ; supplemental material available online with this article; https://doi.org/10.1172/JCI91512DS1 ). These observations were not entirely surprising, given the paucity of examples of immunogenic D–amino acid retroinversion T cell agonists described to date ( 22 ).…”

Section: Resultsmentioning

confidence: 95%

“…Based on previous reports of occasional cross-recognition (reviewed in ref. 22 ), we initially examined the ability of a retroinversion of the GILGFVFTL epitope ltfvfglig (lower case type used to denote D–amino acids) to activate an archetypal TRBV19 + ( 24 ) HLA-A2–GILGFVFTL–specific CD8 + T cell clone (ALF3). In this particular setting, however, the retroinverted D peptide was not immunogenic ( Supplemental Figure 1A ; supplemental material available online with this article; https://doi.org/10.1172/JCI91512DS1 ).…”

Section: Resultsmentioning

confidence: 99%

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Peptide mimic for influenza vaccination using nonnatural combinatorial chemistry

Miles¹,

Tan²,

Dolton³

et al. 2018

Journal of Clinical Investigation

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Polypeptide vaccines effectively activate human T cells but suffer from poor biological stability, which confines both transport logistics and in vivo therapeutic activity. Synthetic biology has the potential to address these limitations through the generation of highly stable antigenic “mimics” using subunits that do not exist in the natural world. We developed a platform based on D–amino acid combinatorial chemistry and used this platform to reverse engineer a fully artificial CD8+ T cell agonist that mirrored the immunogenicity profile of a native epitope blueprint from influenza virus. This nonnatural peptide was highly stable in human serum and gastric acid, reflecting an intrinsic resistance to physical and enzymatic degradation. In vitro, the synthetic agonist stimulated and expanded an archetypal repertoire of polyfunctional human influenza virus–specific CD8+ T cells. In vivo, specific responses were elicited in naive humanized mice by subcutaneous vaccination, conferring protection from subsequent lethal influenza challenge. Moreover, the synthetic agonist was immunogenic after oral administration. This proof-of-concept study highlights the power of synthetic biology to expand the horizons of vaccine design and therapeutic delivery.

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“…1,2 The differences in the clinical course of HIV-1 infection may correspond to genetic variances in HIV-1 strains, host genetic variances, or differences in the virus-specific immune responses. [3][4][5][6] HIV infection can be divided into three stages: nonprogressive, chronic, and acute infection. It was found that longterm nonprogressive patients carried undetectable viral loads, had normal CD4 + T cell levels, but had virus-specific cellular responses in peripheral blood and mucosal compartments.…”

Section: H Uman Immunodeficiency Virus (Hiv) Is a Lentivirus That Caumentioning

confidence: 99%

Comparison of Transcriptional Profiles Between CD4⁺ and CD8⁺ T Cells in HIV Type 1-Infected Patients

Ye²,

Han³

et al. 2014

AIDS Research and Human Retroviruses

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The CD4+ /CD8 + T cell ratio is altered when HIV-1 infects the human immune system. However, the exact mechanisms of how CD4+ and CD8 + T cells participate in HIV infection are still unknown. This study used bioinformatics methods to compare the transcriptional profiles between CD4+ and CD8 + T cells in HIV-1-infected patients in order to explore the potential molecular mechanisms of CD4 + and CD8 + T cells in HIV-1 infection. We found that expression patterns of differentially expressed genes (DEG) in CD4 + T cells were dramatically different from those in CD8 + T cells. We also constructed protein-protein interaction (PPI) networks to extract functional modules at each stage, and found that some of the important genes such as BRCA1 were central hubs of the modules. Finally, we applied functional annotation to the modules and found that CD4 + /CD8 + T cells played critical roles in regulating the cell cycle and other cellular pathways. Thus, this study would greatly further our understanding of the roles of T cells in HIV infection, and provide potential clues for developing AIDS vaccines in the future.

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Advances in T-Cell Epitope Engineering

Cited by 11 publications

References 46 publications

Naive CD8⁺ T‐cell precursors display structured TCR repertoires and composite antigen‐driven selection dynamics

Naive CD8⁺ T‐cell precursors display structured TCR repertoires and composite antigen‐driven selection dynamics

Peptide mimic for influenza vaccination using nonnatural combinatorial chemistry

Comparison of Transcriptional Profiles Between CD4⁺ and CD8⁺ T Cells in HIV Type 1-Infected Patients

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Advances in T-Cell Epitope Engineering

Cited by 11 publications

References 46 publications

Naive CD8+ T‐cell precursors display structured TCR repertoires and composite antigen‐driven selection dynamics

Naive CD8+ T‐cell precursors display structured TCR repertoires and composite antigen‐driven selection dynamics

Peptide mimic for influenza vaccination using nonnatural combinatorial chemistry

Comparison of Transcriptional Profiles Between CD4+ and CD8+ T Cells in HIV Type 1-Infected Patients

Contact Info

Product

Resources

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Naive CD8⁺ T‐cell precursors display structured TCR repertoires and composite antigen‐driven selection dynamics

Naive CD8⁺ T‐cell precursors display structured TCR repertoires and composite antigen‐driven selection dynamics

Comparison of Transcriptional Profiles Between CD4⁺ and CD8⁺ T Cells in HIV Type 1-Infected Patients