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.
|Number of pages||10|
|State||Published - Jan 2012|
Bibliographical noteFunding Information:
Funding provided through NIH NIAID U01AI77887 , and a grant from the National Natural Science Foundation Project of China (No. 81171604 ).
- HLA-B07 epitopes
- Toxoplasma gondii
ASJC Scopus subject areas
- Immunology and Allergy