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 L Henriquez, Craig W Roberts, Rima McLeod

Research output: Contribution to journalArticlepeer-review

31 Citations (Scopus)

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*07 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.

Original languageEnglish
Pages (from-to)1-10
Number of pages10
JournalHuman Immunology
Volume73
Issue number1
DOIs
Publication statusPublished - Jan 2012

Keywords

  • Adjuvants, Immunologic
  • Amino Acid Sequence
  • Animals
  • CD8-Positive T-Lymphocytes
  • Cell Proliferation
  • Cells, Cultured
  • Enzyme-Linked Immunosorbent Assay
  • Epitopes, T-Lymphocyte
  • Female
  • HLA-B7 Antigen
  • Interferon-gamma
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Peptides
  • T-Lymphocytes
  • T-Lymphocytes, Helper-Inducer
  • Toxoplasma
  • Toxoplasmosis, Animal
  • Vaccination
  • Vaccines, Subunit

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