Toxoplasma gondii HLA-B(⁎)0702-restricted GRA7(20-28) peptide with adjuvants and a universal helper T cell epitope elicits CD8(+) T cells producing interferon-γ and reduces parasite burden in HLA-B(⁎)0702 mice

Hua Cong, Ernest J Mui, William H Witola, John Sidney, Jeff Alexander, Alessandro Sette, Ajesh Maewal, Kamal El Bissati, Ying Zhou, Yasuhiro Suzuki, Daniel Lee, Stuart Woods, Caroline Sommerville, Fiona Henriquez, Craig Roberts, Rima McLeod

Research output: Contribution to journalArticle

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Abstract

The ability of CD8(+) T cells to act as cytolytic effectors and produce interferon-γ (IFN-γ) was demonstrated to mediate resistance to Toxoplasma gondii in murine models because of the recognition of peptides restricted by murine major histocompatibility complex (MHC) class I molecules. However, no T gondii-specific HLA-B07-restricted peptides were proven protective against T gondii. Recently, 2 T gondii-specific HLA-B(⁎)0702-restricted T cell epitopes, GRA7(20-28) (LPQFATAAT) and GRA3(27-35) (VPFVVFLVA), displayed high-affinity binding to HLA-B(⁎)0702 and elicited IFN-γ from peripheral blood mononuclear cells of seropositive HLA-B(⁎)0702 persons. Herein, these peptides were evaluated to determine whether they could elicit IFN-γ in splenocytes of HLA-B(⁎)0702 transgenic mice when administered with adjuvants and protect against subsequent challenge. Peptide-specific IFN-γ-producing T cells were identified by enzyme-linked immunosorbent spot and proliferation assays utilizing splenic T lymphocytes from human lymphocyte antigen (HLA) transgenic mice. When HLA-B(⁎)0702 mice were immunized with one of the identified epitopes, GRA7(20-28) in conjunction with a universal CD4(+) T cell epitope (PADRE) and adjuvants (CD4(+) T cell adjuvant, GLA-SE, and TLR2 stimulatory Pam(2)Cys for CD8(+) T cells), this immunization induced CD8(+) T cells to produce IFN-γ and protected mice against high parasite burden when challenged with T gondii. This work demonstrates the feasibility of bioinformatics followed by an empiric approach based on HLA binding to test this biologic activity for identifying protective HLA-B(⁎)0702-restricted T gondii peptides and adjuvants that elicit protective immune responses in HLA-B(⁎)0702 mice.
LanguageEnglish
Pages1-10
Number of pages10
JournalHuman Immunology
Volume73
Issue number1
DOIs
Publication statusPublished - Jan 2012

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T-Lymphocyte Epitopes
Toxoplasma
Helper-Inducer T-Lymphocytes
Interferon-gamma
Parasites
Lymphocytes
T-Lymphocytes
Antigens
Peptides
Transgenic Mice
Peptide T
Immunosorbents
Computational Biology
Major Histocompatibility Complex
Epitopes
Immunization
Blood Cells

Keywords

  • toxoplasma gondii
  • vaccine
  • adjuvant
  • PADRE
  • epitopes

Cite this

Cong, Hua ; Mui, Ernest J ; Witola, William H ; Sidney, John ; Alexander, Jeff ; Sette, Alessandro ; Maewal, Ajesh ; El Bissati, Kamal ; Zhou, Ying ; Suzuki, Yasuhiro ; Lee, Daniel ; Woods, Stuart ; Sommerville, Caroline ; Henriquez, Fiona ; Roberts, Craig ; McLeod, Rima. / Toxoplasma gondii HLA-B(⁎)0702-restricted GRA7(20-28) peptide with adjuvants and a universal helper T cell epitope elicits CD8(+) T cells producing interferon-γ and reduces parasite burden in HLA-B(⁎)0702 mice. In: Human Immunology. 2012 ; Vol. 73, No. 1. pp. 1-10.
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abstract = "The ability of CD8(+) T cells to act as cytolytic effectors and produce interferon-γ (IFN-γ) was demonstrated to mediate resistance to Toxoplasma gondii in murine models because of the recognition of peptides restricted by murine major histocompatibility complex (MHC) class I molecules. However, no T gondii-specific HLA-B07-restricted peptides were proven protective against T gondii. Recently, 2 T gondii-specific HLA-B(⁎)0702-restricted T cell epitopes, GRA7(20-28) (LPQFATAAT) and GRA3(27-35) (VPFVVFLVA), displayed high-affinity binding to HLA-B(⁎)0702 and elicited IFN-γ from peripheral blood mononuclear cells of seropositive HLA-B(⁎)0702 persons. Herein, these peptides were evaluated to determine whether they could elicit IFN-γ in splenocytes of HLA-B(⁎)0702 transgenic mice when administered with adjuvants and protect against subsequent challenge. Peptide-specific IFN-γ-producing T cells were identified by enzyme-linked immunosorbent spot and proliferation assays utilizing splenic T lymphocytes from human lymphocyte antigen (HLA) transgenic mice. When HLA-B(⁎)0702 mice were immunized with one of the identified epitopes, GRA7(20-28) in conjunction with a universal CD4(+) T cell epitope (PADRE) and adjuvants (CD4(+) T cell adjuvant, GLA-SE, and TLR2 stimulatory Pam(2)Cys for CD8(+) T cells), this immunization induced CD8(+) T cells to produce IFN-γ and protected mice against high parasite burden when challenged with T gondii. This work demonstrates the feasibility of bioinformatics followed by an empiric approach based on HLA binding to test this biologic activity for identifying protective HLA-B(⁎)0702-restricted T gondii peptides and adjuvants that elicit protective immune responses in HLA-B(⁎)0702 mice.",
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Toxoplasma gondii HLA-B(⁎)0702-restricted GRA7(20-28) peptide with adjuvants and a universal helper T cell epitope elicits CD8(+) T cells producing interferon-γ and reduces parasite burden in HLA-B(⁎)0702 mice. / Cong, Hua; Mui, Ernest J; Witola, William H; Sidney, John; Alexander, Jeff; Sette, Alessandro; Maewal, Ajesh; El Bissati, Kamal; Zhou, Ying; Suzuki, Yasuhiro; Lee, Daniel; Woods, Stuart; Sommerville, Caroline; Henriquez, Fiona; Roberts, Craig; McLeod, Rima.

In: Human Immunology, Vol. 73, No. 1, 01.2012, p. 1-10.

Research output: Contribution to journalArticle

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AU - Cong, Hua

AU - Mui, Ernest J

AU - Witola, William H

AU - Sidney, John

AU - Alexander, Jeff

AU - Sette, Alessandro

AU - Maewal, Ajesh

AU - El Bissati, Kamal

AU - Zhou, Ying

AU - Suzuki, Yasuhiro

AU - Lee, Daniel

AU - Woods, Stuart

AU - Sommerville, Caroline

AU - Henriquez, Fiona

AU - Roberts, Craig

AU - McLeod, Rima

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KW - toxoplasma gondii

KW - vaccine

KW - adjuvant

KW - PADRE

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