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

39 Scopus citations

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 2Cys 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
StatePublished - Jan 2012

Bibliographical note

Funding Information:
Funding provided through NIH NIAID U01AI77887 , and a grant from the National Natural Science Foundation Project of China (No. 81171604 ).

Keywords

  • Adjuvant
  • HLA-B07 epitopes
  • PADRE
  • Toxoplasma gondii
  • Vaccine

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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