Identification of peptides from human pathogens able to cross‐activate an HIV‐1‐gag‐specific CD4<sup>+</sup> T cell clone

Venturini, Sara; Allicotti, Gina; Zhao, Yindong; Simon, Richard; Burton, Dennis R.; Pinilla, Clemencia; Poignard, Pascal

doi:10.1002/eji.200425767

Cited by 6 publications

(3 citation statements)

References 40 publications

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“…Our previous studies on T cell pathogen specificity have shown that more than one peptide can be recognized by a single pathogen specific T cell clone [47], [49], [52]. However, this was not the case in this work in which only one vaccinia epitope was found to stimulate each of the clones.…”

Section: Discussioncontrasting

confidence: 66%

GM-CSF Production Allows the Identification of Immunoprevalent Antigens Recognized by Human CD4+ T Cells Following Smallpox Vaccination

Judkowski

Bunying

et al. 2011

PLoS ONE

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The threat of bioterrorism with smallpox and the broad use of vaccinia vectors for other vaccines have led to the resurgence in the study of vaccinia immunological memory. The importance of the role of CD4+ T cells in the control of vaccinia infection is well known. However, more CD8+ than CD4+ T cell epitopes recognized by human subjects immunized with vaccinia virus have been reported. This could be, in part, due to the fact that most of the studies that have identified human CD4+ specific protein-derived fragments or peptides have used IFN-γ production to evaluate vaccinia specific T cell responses. Based on these findings, we reasoned that analyzing a large panel of cytokines would permit us to generate a more complete analysis of the CD4 T cell responses. The results presented provide clear evidence that TNF-α is an excellent readout of vaccinia specificity and that other cytokines such as GM-CSF can be used to evaluate the reactivity of CD4+ T cells in response to vaccinia antigens. Furthermore, using these cytokines as readout of vaccinia specificity, we present the identification of novel peptides from immunoprevalent vaccinia proteins recognized by CD4+ T cells derived from smallpox vaccinated human subjects. In conclusion, we describe a “T cell–driven” methodology that can be implemented to determine the specificity of the T cell response upon vaccination or infection. Together, the single pathogen in vitro stimulation, the selection of CD4+ T cells specific to the pathogen by limiting dilution, the evaluation of pathogen specificity by detecting multiple cytokines, and the screening of the clones with synthetic combinatorial libraries, constitutes a novel and valuable approach for the elucidation of human CD4+ T cell specificity in response to large pathogens.

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Section: Discussioncontrasting

confidence: 66%

GM-CSF Production Allows the Identification of Immunoprevalent Antigens Recognized by Human CD4+ T Cells Following Smallpox Vaccination

Judkowski

Bunying

et al. 2011

PLoS ONE

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“…In contrast to the genetic screen described here, which identifies single amino acid substitution APLs, PS-SCL screens peptides that are randomized at every position except one. While PS-SCL scanning has been shown capable of identifying superagonist analogs (25, 26), the need to deduce the sequence of the putative superagonists, and the subsequent testing of large numbers of potentially nonproductive altered peptide ligands which are non-cross-reactive for the native eptiope, present additional hurdles.…”

Section: Discussionmentioning

confidence: 99%

Conditional Superagonist CTL Ligands for the Promotion of Tumor-Specific CTL Responses

Abdul-Alim

Yee

2010

The Journal of Immunology

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While it has been demonstrated that cytotoxic T lymphocytes (CTL) can be raised against tumor-associated self-antigens, achieving consistent and effective clinical responses has proven challenging. Superagonist altered peptide ligands (APL) can often elicit potent anti-tumor CTL responses where the native tumor-associated epitope fails. Current methods have identified a limited number of superagonist APLs, including the prototypic 27L mutant of MART-1. However, more comprehensive screening strategies would be desirable. In this study we utilize a novel genetic screen, involving recombinant technology and class I antigen cross-presentation, to search for supraoptimal superagonists of the 27L MART-1 mutant by surveying the effectiveness of virtually every single amino acid substitution mutant of 27L to activate human antigen-specific CTL clones recognizing the wild-type MART-126-35 epitope. We identify 3 novel mutant epitopes with superagonist properties that are functionally superior to 27L; however, the ability of a given analog to act as superagonist varies among patients and suggest that a given superagonist altered peptide ligand may be ideally suited to different patients. These findings endorse the use of comprehensive methods to establish panels of potential superagonist APLs to individualize tumor peptide vaccines among patients.

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“…Without contact with allogeneic MHC molecules, the exposure to commensal bacteria or environmental antigens is also probably to induce potent heterologous immunity, which is one way for the generation of alloreactive memory T cells (23,24). Many studies have identified that alloreactive T-cell clones can also stem from other immune events (25,26), such as dozens of virus-specific (CMV, EBV, Flu, HIV, Zika Virus, SARS-CoV-2) memory T cells that show cross-reactivity to allogeneic pMHC complexes (27)(28)(29)(30)(31)(32). Thereby, these memory T cells can also pre-exist in the host even if they have not previously encountered donor-derived antigens.…”

Section: T Cells In Transplantationmentioning

confidence: 99%

Analysis of T-Cell Receptor Repertoire in Transplantation: Fingerprint of T Cell-mediated Alloresponse

Tian

2022

Front. Immunol.

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T cells play a key role in determining allograft function by mediating allogeneic immune responses to cause rejection, and recent work pointed their role in mediating tolerance in transplantation. The unique T-cell receptor (TCR) expressed on the surface of each T cell determines the antigen specificity of the cell and can be the specific fingerprint for identifying and monitoring. Next-generation sequencing (NGS) techniques provide powerful tools for deep and high-throughput TCR profiling, and facilitate to depict the entire T cell repertoire profile and trace antigen-specific T cells in circulation and local tissues. Tailing T cell transcriptomes and TCR sequences at the single cell level provides a full landscape of alloreactive T-cell clones development and biofunction in alloresponse. Here, we review the recent advances in TCR sequencing techniques and computational tools, as well as the recent discovery in overall TCR profile and antigen-specific T cells tracking in transplantation. We further discuss the challenges and potential of using TCR sequencing-based assays to profile alloreactive TCR repertoire as the fingerprint for immune monitoring and prediction of rejection and tolerance.

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Identification of peptides from human pathogens able to cross‐activate an HIV‐1‐gag‐specific CD4⁺ T cell clone

Cited by 6 publications

References 40 publications

GM-CSF Production Allows the Identification of Immunoprevalent Antigens Recognized by Human CD4+ T Cells Following Smallpox Vaccination

GM-CSF Production Allows the Identification of Immunoprevalent Antigens Recognized by Human CD4+ T Cells Following Smallpox Vaccination

Conditional Superagonist CTL Ligands for the Promotion of Tumor-Specific CTL Responses

Analysis of T-Cell Receptor Repertoire in Transplantation: Fingerprint of T Cell-mediated Alloresponse

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Identification of peptides from human pathogens able to cross‐activate an HIV‐1‐gag‐specific CD4+ T cell clone

Cited by 6 publications

References 40 publications

GM-CSF Production Allows the Identification of Immunoprevalent Antigens Recognized by Human CD4+ T Cells Following Smallpox Vaccination

GM-CSF Production Allows the Identification of Immunoprevalent Antigens Recognized by Human CD4+ T Cells Following Smallpox Vaccination

Conditional Superagonist CTL Ligands for the Promotion of Tumor-Specific CTL Responses

Analysis of T-Cell Receptor Repertoire in Transplantation: Fingerprint of T Cell-mediated Alloresponse

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Identification of peptides from human pathogens able to cross‐activate an HIV‐1‐gag‐specific CD4⁺ T cell clone