Antigenicity of HIV-derived T helper determinants in the context of carrier recombinant proteins

Effect on T helper cell repertoire selection

Fabrizio Manca, Piergiuseppe De Berardinis, Daniela Fenoglio, Maria Neve Ombra, Giuseppina Li Pira, Daniele Saverino, Monica Autiero, Luisa Lozzi, Luisa Bracci, John Guardiola

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

T helper (Th) epitopes can be included in a recombinant protein with B and CTL epitopes to create more effective immunogens. To determine whether the antigenicity of HIV Th epitopes is preserved in this altered molecular context, human Th clones specific for peptides of HIV gp120 and reverse transcriptase p66 were challenged with recombinant proteins carrying the antigenic epitopes in different sites. We found that a given epitope was recognized by a specific T cell clone only when it was inserted in a particular position of the carrier. However, the permissive position was not the same for all epitopes. Enzymatic excision from a nonpermissive context or insertion of a polyserine spacer between the epitope and the carrier restored antigenicity. Nevertheless, antigenicity was not abolished in a synthetic peptide encompassing the epitope and the neighboring residues from the nonpermissive location. These data suggest that, in this case, the primary sequence of the chimeric protein flanking the HIV peptide is not responsible for loss of antigenicity. Furthermore, constructs carrying the epitope in a given position were recognized by peptide-specific Th clones raised from some individuals, but not from others. We show that this is due neither to individual modes of processing nor to the use of distinct major histocompatibility complex MHC class II restriction elements, but rather that it is related to the fine specificity of the clones. To study the effect of epitope context on selection of T cell repertoire in a naive individual, T cell lines were generated in vitro by stimulation with different peptide constructs. This resulted in the induction of diverse clonotypes defined by the pattern of recognition of different constructs, by T cell receptor Vβ gene usage and by fine epitope mapping.

Original languageEnglish
Pages (from-to)2461-2469
Number of pages9
JournalEuropean Journal of Immunology
Volume26
Issue number10
DOIs
Publication statusPublished - 1996

Fingerprint

Helper-Inducer T-Lymphocytes
Recombinant Proteins
Epitopes
Carrier Proteins
HIV
Clone Cells
Peptides
T-Lymphocytes
Human Immunodeficiency Virus Proteins
Peptide T
Epitope Mapping
HIV Reverse Transcriptase
T-Cell Receptor Genes
Major Histocompatibility Complex
Cell Line

Keywords

  • Antigen processing
  • Chimeric antigen
  • HIV
  • Repertoire selection
  • T helper epitope

ASJC Scopus subject areas

  • Immunology

Cite this

Antigenicity of HIV-derived T helper determinants in the context of carrier recombinant proteins : Effect on T helper cell repertoire selection. / Manca, Fabrizio; De Berardinis, Piergiuseppe; Fenoglio, Daniela; Ombra, Maria Neve; Li Pira, Giuseppina; Saverino, Daniele; Autiero, Monica; Lozzi, Luisa; Bracci, Luisa; Guardiola, John.

In: European Journal of Immunology, Vol. 26, No. 10, 1996, p. 2461-2469.

Research output: Contribution to journalArticle

Manca, Fabrizio ; De Berardinis, Piergiuseppe ; Fenoglio, Daniela ; Ombra, Maria Neve ; Li Pira, Giuseppina ; Saverino, Daniele ; Autiero, Monica ; Lozzi, Luisa ; Bracci, Luisa ; Guardiola, John. / Antigenicity of HIV-derived T helper determinants in the context of carrier recombinant proteins : Effect on T helper cell repertoire selection. In: European Journal of Immunology. 1996 ; Vol. 26, No. 10. pp. 2461-2469.
@article{fb77351904e549898e1f0bd2ac2a0fec,
title = "Antigenicity of HIV-derived T helper determinants in the context of carrier recombinant proteins: Effect on T helper cell repertoire selection",
abstract = "T helper (Th) epitopes can be included in a recombinant protein with B and CTL epitopes to create more effective immunogens. To determine whether the antigenicity of HIV Th epitopes is preserved in this altered molecular context, human Th clones specific for peptides of HIV gp120 and reverse transcriptase p66 were challenged with recombinant proteins carrying the antigenic epitopes in different sites. We found that a given epitope was recognized by a specific T cell clone only when it was inserted in a particular position of the carrier. However, the permissive position was not the same for all epitopes. Enzymatic excision from a nonpermissive context or insertion of a polyserine spacer between the epitope and the carrier restored antigenicity. Nevertheless, antigenicity was not abolished in a synthetic peptide encompassing the epitope and the neighboring residues from the nonpermissive location. These data suggest that, in this case, the primary sequence of the chimeric protein flanking the HIV peptide is not responsible for loss of antigenicity. Furthermore, constructs carrying the epitope in a given position were recognized by peptide-specific Th clones raised from some individuals, but not from others. We show that this is due neither to individual modes of processing nor to the use of distinct major histocompatibility complex MHC class II restriction elements, but rather that it is related to the fine specificity of the clones. To study the effect of epitope context on selection of T cell repertoire in a naive individual, T cell lines were generated in vitro by stimulation with different peptide constructs. This resulted in the induction of diverse clonotypes defined by the pattern of recognition of different constructs, by T cell receptor Vβ gene usage and by fine epitope mapping.",
keywords = "Antigen processing, Chimeric antigen, HIV, Repertoire selection, T helper epitope",
author = "Fabrizio Manca and {De Berardinis}, Piergiuseppe and Daniela Fenoglio and Ombra, {Maria Neve} and {Li Pira}, Giuseppina and Daniele Saverino and Monica Autiero and Luisa Lozzi and Luisa Bracci and John Guardiola",
year = "1996",
doi = "10.1002/eji.1830261029",
language = "English",
volume = "26",
pages = "2461--2469",
journal = "European Journal of Immunology",
issn = "0014-2980",
publisher = "wiley",
number = "10",

}

TY - JOUR

T1 - Antigenicity of HIV-derived T helper determinants in the context of carrier recombinant proteins

T2 - Effect on T helper cell repertoire selection

AU - Manca, Fabrizio

AU - De Berardinis, Piergiuseppe

AU - Fenoglio, Daniela

AU - Ombra, Maria Neve

AU - Li Pira, Giuseppina

AU - Saverino, Daniele

AU - Autiero, Monica

AU - Lozzi, Luisa

AU - Bracci, Luisa

AU - Guardiola, John

PY - 1996

Y1 - 1996

N2 - T helper (Th) epitopes can be included in a recombinant protein with B and CTL epitopes to create more effective immunogens. To determine whether the antigenicity of HIV Th epitopes is preserved in this altered molecular context, human Th clones specific for peptides of HIV gp120 and reverse transcriptase p66 were challenged with recombinant proteins carrying the antigenic epitopes in different sites. We found that a given epitope was recognized by a specific T cell clone only when it was inserted in a particular position of the carrier. However, the permissive position was not the same for all epitopes. Enzymatic excision from a nonpermissive context or insertion of a polyserine spacer between the epitope and the carrier restored antigenicity. Nevertheless, antigenicity was not abolished in a synthetic peptide encompassing the epitope and the neighboring residues from the nonpermissive location. These data suggest that, in this case, the primary sequence of the chimeric protein flanking the HIV peptide is not responsible for loss of antigenicity. Furthermore, constructs carrying the epitope in a given position were recognized by peptide-specific Th clones raised from some individuals, but not from others. We show that this is due neither to individual modes of processing nor to the use of distinct major histocompatibility complex MHC class II restriction elements, but rather that it is related to the fine specificity of the clones. To study the effect of epitope context on selection of T cell repertoire in a naive individual, T cell lines were generated in vitro by stimulation with different peptide constructs. This resulted in the induction of diverse clonotypes defined by the pattern of recognition of different constructs, by T cell receptor Vβ gene usage and by fine epitope mapping.

AB - T helper (Th) epitopes can be included in a recombinant protein with B and CTL epitopes to create more effective immunogens. To determine whether the antigenicity of HIV Th epitopes is preserved in this altered molecular context, human Th clones specific for peptides of HIV gp120 and reverse transcriptase p66 were challenged with recombinant proteins carrying the antigenic epitopes in different sites. We found that a given epitope was recognized by a specific T cell clone only when it was inserted in a particular position of the carrier. However, the permissive position was not the same for all epitopes. Enzymatic excision from a nonpermissive context or insertion of a polyserine spacer between the epitope and the carrier restored antigenicity. Nevertheless, antigenicity was not abolished in a synthetic peptide encompassing the epitope and the neighboring residues from the nonpermissive location. These data suggest that, in this case, the primary sequence of the chimeric protein flanking the HIV peptide is not responsible for loss of antigenicity. Furthermore, constructs carrying the epitope in a given position were recognized by peptide-specific Th clones raised from some individuals, but not from others. We show that this is due neither to individual modes of processing nor to the use of distinct major histocompatibility complex MHC class II restriction elements, but rather that it is related to the fine specificity of the clones. To study the effect of epitope context on selection of T cell repertoire in a naive individual, T cell lines were generated in vitro by stimulation with different peptide constructs. This resulted in the induction of diverse clonotypes defined by the pattern of recognition of different constructs, by T cell receptor Vβ gene usage and by fine epitope mapping.

KW - Antigen processing

KW - Chimeric antigen

KW - HIV

KW - Repertoire selection

KW - T helper epitope

UR - http://www.scopus.com/inward/record.url?scp=10244278019&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=10244278019&partnerID=8YFLogxK

U2 - 10.1002/eji.1830261029

DO - 10.1002/eji.1830261029

M3 - Article

VL - 26

SP - 2461

EP - 2469

JO - European Journal of Immunology

JF - European Journal of Immunology

SN - 0014-2980

IS - 10

ER -