Exploring immunological specificity using synthetic peptide combinatorial libraries

Pinilla, Clemencia; Martin, Roland; Gran, Bruno; Appel, Jon R.; Boggiano, César; Wilson, Darcy B.; Houghten, Richard A.

doi:10.1016/s0952-7915(99)80033-8

Cited by 98 publications

(68 citation statements)

References 55 publications

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“…This study adds a new and important contribution to the definition and prediction of T cell epitopes using synthetic combinatorial libraries (26,27). It should be noted that many of the previous approaches to the identification of T cell epitopes were based on the prediction of which peptides would be good binders for specific MHC/HLA molecules (8,16).…”

Section: Discussionmentioning

confidence: 93%

“…A role for degenerate T cell recognition has been postulated for such diverse immunological phenomena as thymic selection (48), peripheral T cell survival (49), protection from infectious diseases, and induction of autoimmunity (49,50). It was previously shown that peptide combinatorial libraries in the positional scanning format can be used to define the spectrum of agonist ligands for clonotypic TCR (26,49). In recent studies, we showed that functional responses elicited in CD4 ϩ TCC by PS-SCL could be used to build motifs for database searches and thus identify a spectrum of ligands of different potency for clonotypic TCR (45,46).…”

Section: Discussionmentioning

confidence: 99%

“…The development of soluble-and bead-bound combinatorial peptide libraries in various formats representing millions to trillions of peptides has emerged as a powerful approach to both T cell epitope determination and the analysis of TCR specificity and flexibility, as recently reviewed (26,27). Recent studies (28 -32) of T cell clones (TCC) 5 demonstrated the efficacy of using positional scanning synthetic combinatorial libraries (PS-SCL) for identifying target Ags and highly active peptide mimics.…”

Section: T He Cd8mentioning

confidence: 99%

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Combinatorial Peptide Libraries and Biometric Score Matrices Permit the Quantitative Analysis of Specific and Degenerate Interactions Between Clonotypic TCR and MHC Peptide Ligands

Zhao¹,

Gran

Pinilla

et al. 2001

The Journal of Immunology

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122

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The interaction of TCRs with MHC peptide ligands can be highly flexible, so that many different peptides are recognized by the same TCR in the context of a single restriction element. We provide a quantitative description of such interactions, which allows the identification of T cell epitopes and molecular mimics. The response of T cell clones to positional scanning synthetic combinatorial libraries is analyzed with a mathematical approach that is based on a model of independent contribution of individual amino acids to peptide Ag recognition. This biometric analysis compares the information derived from these libraries composed of trillions of decapeptides with all the millions of decapeptides contained in a protein database to rank and predict the most stimulatory peptides for a given T cell clone. We demonstrate the predictive power of the novel strategy and show that, together with gene expression profiling by cDNA microarrays, it leads to the identification of novel candidate autoantigens in the inflammatory autoimmune disease, multiple sclerosis.

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Section: Discussionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Section: T He Cd8mentioning

confidence: 99%

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Combinatorial Peptide Libraries and Biometric Score Matrices Permit the Quantitative Analysis of Specific and Degenerate Interactions Between Clonotypic TCR and MHC Peptide Ligands

Zhao¹,

Gran

Pinilla

et al. 2001

The Journal of Immunology

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122

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“…In this study, based on a decapeptide PS-SCL biometrical analysis [16,[20][21][22], we selected and synthesized 122 potential peptide ligands of an HIV-1 gag-specific TCC originally obtained from an HIV-1-negative donor by in vitro immunization [7]. Several peptides, all confirmed to be active, were HIV-1 peptides variants of the same region of gag from different viral strains.…”

Section: Discussionmentioning

confidence: 99%

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

Venturini¹,

Allicotti²,

Zhao³

et al. 2005

Eur J Immunol

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Antigen recognition by T cells is degenerate both at the MHC and the TCR level. In this study, we analyzed the cross‐reactivity of a human HIV‐1 gag p24‐specific CD4+ T cell clone obtained from an HIV‐1‐seronegative donor using a positional scanning synthetic combinatorial peptide library (PS‐SCL)‐based biometrical analysis. A number of decapeptides able to activate the HIV‐1 gag‐specific clone were identified and shown to correspond to sequences found in other human pathogens. Two of these peptides activated the T cell clone with the same stimulatory potency as the original HIV‐1 gag p24 peptide. These findings show that an HIV‐1‐specific human T helper clone can react efficiently with peptides from other pathogens and suggest that cellular immune responses identified as being specific for one human pathogen (HIV‐1) could arise from exposure to other pathogens.

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“…These mutants were identified using a positional scanning synthetic combinatorial library (PS-SCL) approach alone [15] or in combination with a biometrical analysis that uses the data generated by screening a PS-SCL to analyze and rank all peptides in a protein database for sequences with high predicted reactivity [16]. These approaches allowed us to identify epitope mimics that induce SL9-specific responses in HLA-A2-transgenic mice and that are widely crossreactive with human PBMC from HLA-A*0201-expressing, HIV-infected individuals.…”

Section: Introductionmentioning

confidence: 99%

Discovery and characterization of highly immunogenic and broadly recognized mimics of the HIV‐1 CTL epitope Gag_77–85

et al. 2005

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Human immunodeficiency virus (HIV)-specific cytotoxic T lymphocytes (CTL) play an important role in HIV infection. Given the viral genetic diversity, the selection of suitable antigens and epitope variants will be important in the design of an effective vaccine. We have previously shown that combinatorial libraries are useful tools to identify epitope mimics as well as potentially cross-reactive natural sequences in protein databases. We have applied this approach to the HIV Gag p17-derived epitope SL9 (SLYNTVATL) to identify broadly recognized SL9 mimics and to assess the cross-recognition of naturally occurring SL9 variants. Nine nonapeptides were identified that were up to one order of magnitude more effective than SL9 in stimulating CTL responses in PBMC from HIVinfected subjects. Using transgenic mice, we demonstrate that a number of these epitope mimics were able to generate de novo T cell responses that cross-reacted with the original SL9 sequence. Particularly, mimics with changes at the relatively conserved Fpocket anchor residue were frequently cross-recognized. This approach may lead to vaccine candidates with higher in vivo immunogenicity and increased potential for cross-recognition of naturally occurring SL9 variants.

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Exploring immunological specificity using synthetic peptide combinatorial libraries

Cited by 98 publications

References 55 publications

Combinatorial Peptide Libraries and Biometric Score Matrices Permit the Quantitative Analysis of Specific and Degenerate Interactions Between Clonotypic TCR and MHC Peptide Ligands

Combinatorial Peptide Libraries and Biometric Score Matrices Permit the Quantitative Analysis of Specific and Degenerate Interactions Between Clonotypic TCR and MHC Peptide Ligands

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

Discovery and characterization of highly immunogenic and broadly recognized mimics of the HIV‐1 CTL epitope Gag_77–85

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Exploring immunological specificity using synthetic peptide combinatorial libraries

Cited by 98 publications

References 55 publications

Combinatorial Peptide Libraries and Biometric Score Matrices Permit the Quantitative Analysis of Specific and Degenerate Interactions Between Clonotypic TCR and MHC Peptide Ligands

Combinatorial Peptide Libraries and Biometric Score Matrices Permit the Quantitative Analysis of Specific and Degenerate Interactions Between Clonotypic TCR and MHC Peptide Ligands

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

Discovery and characterization of highly immunogenic and broadly recognized mimics of the HIV‐1 CTL epitope Gag77–85

Contact Info

Product

Resources

About

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

Discovery and characterization of highly immunogenic and broadly recognized mimics of the HIV‐1 CTL epitope Gag_77–85