Hypervariable epitope construct: A synthetic immunogen that overcomes MHC restriction of antigen presentation

Debra Meyer, Jose V Torres

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Vaccines are not universal in their ability to induce favorable immune responses in all individuals because the major histocompatibility complex (MHC) molecules needed for presentation of vaccine components to T cells are limited in the peptides they recognize and bind. A heterogeneous cocktail of related peptides synthesized simultaneously and representing amino acids 414- 434 of the SIV envelope protein was used to induce immune responses stronger than those induced by a single T cell peptide synthesized conventionally and representing the same region of the viral envelope. The heterogeneous peptide mixture called a hypervariable epitope construct (HEC) was capable of overcoming MHC restriction in peptide presentation in four different inbred mouse strains, including a strain that was a poor responder to the AA 414-434 single sequence peptide (SSP). HEC induced proliferation responses 15 times better than those induced by SSP. Antibodies elicited by HEC but not SSP immunization effectively bind viral antigen. The 414-434 HEC and the 414-434 SSP were also tested for their ability to upregulate the expression of MHC class I molecules on the surface of the mutant RMA-S murine cell line. Surface display of MHC molecules was measured by confocal microscopy followed by calculation of fluorescence intensity of images. HECs upregulated expression of MHC molecules 30% more than SSP peptides. Our findings suggest that HEC cocktails could be effective components of subunit vaccines to help overcome the unresponsiveness observed in outbred animals and in humans as a result of MHC-restricted antigen presentation.

Original languageEnglish (US)
Pages (from-to)631-637
Number of pages7
JournalMolecular Immunology
Volume36
Issue number10
DOIs
StatePublished - Jul 1999

Fingerprint

Synthetic Vaccines
Antigen Presentation
Major Histocompatibility Complex
Epitopes
Peptides
Vaccines
T-Lymphocytes
Subunit Vaccines
Inbred Strains Mice
Viral Antigens
Confocal Microscopy
Immunization
Up-Regulation
Fluorescence

Keywords

  • AIDS
  • HEC
  • MHC restriction
  • Peptide immunogen
  • Vaccine

ASJC Scopus subject areas

  • Molecular Biology
  • Immunology

Cite this

Hypervariable epitope construct : A synthetic immunogen that overcomes MHC restriction of antigen presentation. / Meyer, Debra; Torres, Jose V.

In: Molecular Immunology, Vol. 36, No. 10, 07.1999, p. 631-637.

Research output: Contribution to journalArticle

@article{b9817a1f77f24f81b036b8594d5d0ef1,
title = "Hypervariable epitope construct: A synthetic immunogen that overcomes MHC restriction of antigen presentation",
abstract = "Vaccines are not universal in their ability to induce favorable immune responses in all individuals because the major histocompatibility complex (MHC) molecules needed for presentation of vaccine components to T cells are limited in the peptides they recognize and bind. A heterogeneous cocktail of related peptides synthesized simultaneously and representing amino acids 414- 434 of the SIV envelope protein was used to induce immune responses stronger than those induced by a single T cell peptide synthesized conventionally and representing the same region of the viral envelope. The heterogeneous peptide mixture called a hypervariable epitope construct (HEC) was capable of overcoming MHC restriction in peptide presentation in four different inbred mouse strains, including a strain that was a poor responder to the AA 414-434 single sequence peptide (SSP). HEC induced proliferation responses 15 times better than those induced by SSP. Antibodies elicited by HEC but not SSP immunization effectively bind viral antigen. The 414-434 HEC and the 414-434 SSP were also tested for their ability to upregulate the expression of MHC class I molecules on the surface of the mutant RMA-S murine cell line. Surface display of MHC molecules was measured by confocal microscopy followed by calculation of fluorescence intensity of images. HECs upregulated expression of MHC molecules 30{\%} more than SSP peptides. Our findings suggest that HEC cocktails could be effective components of subunit vaccines to help overcome the unresponsiveness observed in outbred animals and in humans as a result of MHC-restricted antigen presentation.",
keywords = "AIDS, HEC, MHC restriction, Peptide immunogen, Vaccine",
author = "Debra Meyer and Torres, {Jose V}",
year = "1999",
month = "7",
doi = "10.1016/S0161-5890(99)00080-2",
language = "English (US)",
volume = "36",
pages = "631--637",
journal = "Molecular Immunology",
issn = "0161-5890",
publisher = "Elsevier Limited",
number = "10",

}

TY - JOUR

T1 - Hypervariable epitope construct

T2 - A synthetic immunogen that overcomes MHC restriction of antigen presentation

AU - Meyer, Debra

AU - Torres, Jose V

PY - 1999/7

Y1 - 1999/7

N2 - Vaccines are not universal in their ability to induce favorable immune responses in all individuals because the major histocompatibility complex (MHC) molecules needed for presentation of vaccine components to T cells are limited in the peptides they recognize and bind. A heterogeneous cocktail of related peptides synthesized simultaneously and representing amino acids 414- 434 of the SIV envelope protein was used to induce immune responses stronger than those induced by a single T cell peptide synthesized conventionally and representing the same region of the viral envelope. The heterogeneous peptide mixture called a hypervariable epitope construct (HEC) was capable of overcoming MHC restriction in peptide presentation in four different inbred mouse strains, including a strain that was a poor responder to the AA 414-434 single sequence peptide (SSP). HEC induced proliferation responses 15 times better than those induced by SSP. Antibodies elicited by HEC but not SSP immunization effectively bind viral antigen. The 414-434 HEC and the 414-434 SSP were also tested for their ability to upregulate the expression of MHC class I molecules on the surface of the mutant RMA-S murine cell line. Surface display of MHC molecules was measured by confocal microscopy followed by calculation of fluorescence intensity of images. HECs upregulated expression of MHC molecules 30% more than SSP peptides. Our findings suggest that HEC cocktails could be effective components of subunit vaccines to help overcome the unresponsiveness observed in outbred animals and in humans as a result of MHC-restricted antigen presentation.

AB - Vaccines are not universal in their ability to induce favorable immune responses in all individuals because the major histocompatibility complex (MHC) molecules needed for presentation of vaccine components to T cells are limited in the peptides they recognize and bind. A heterogeneous cocktail of related peptides synthesized simultaneously and representing amino acids 414- 434 of the SIV envelope protein was used to induce immune responses stronger than those induced by a single T cell peptide synthesized conventionally and representing the same region of the viral envelope. The heterogeneous peptide mixture called a hypervariable epitope construct (HEC) was capable of overcoming MHC restriction in peptide presentation in four different inbred mouse strains, including a strain that was a poor responder to the AA 414-434 single sequence peptide (SSP). HEC induced proliferation responses 15 times better than those induced by SSP. Antibodies elicited by HEC but not SSP immunization effectively bind viral antigen. The 414-434 HEC and the 414-434 SSP were also tested for their ability to upregulate the expression of MHC class I molecules on the surface of the mutant RMA-S murine cell line. Surface display of MHC molecules was measured by confocal microscopy followed by calculation of fluorescence intensity of images. HECs upregulated expression of MHC molecules 30% more than SSP peptides. Our findings suggest that HEC cocktails could be effective components of subunit vaccines to help overcome the unresponsiveness observed in outbred animals and in humans as a result of MHC-restricted antigen presentation.

KW - AIDS

KW - HEC

KW - MHC restriction

KW - Peptide immunogen

KW - Vaccine

UR - http://www.scopus.com/inward/record.url?scp=0032827476&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032827476&partnerID=8YFLogxK

U2 - 10.1016/S0161-5890(99)00080-2

DO - 10.1016/S0161-5890(99)00080-2

M3 - Article

C2 - 10509814

AN - SCOPUS:0032827476

VL - 36

SP - 631

EP - 637

JO - Molecular Immunology

JF - Molecular Immunology

SN - 0161-5890

IS - 10

ER -