The Toxoplasma gondii peptide AS15 elicits CD4 T cells that can control parasite burden.
The apicomplexan parasite Toxoplasma gondii can cause severe disease in immunocompromised individuals. Previous studies in mice have focused largely on CD8(+) T cells, and the role of CD4 T cells is relatively unexplored. Here, we show that immunization of the C57BL/6 strain of mice, in which the immunodominant CD8 T cell response to the parasite dense-granule protein GRA6 cannot be generated, leads to a prominent CD4 T cell response. To identify the CD4 T cell-stimulating antigens, we generated a T. gondii-specific, lacZ-inducible, CD4 T cell hybridoma and used it as a probe to screen a T. gondii cDNA library. We isolated a cDNA encoding a protein of unknown function that we call CD4Ag28m and identified the minimal peptide, AS15, which was presented by major histocompatibility complex (MHC) class II molecules to the CD4 T cells. Immunization of mice with the AS15 peptide provided significant protection against subsequent parasite challenge, resulting in a lower parasite burden in the brain. Our findings identify the first CD4 T cell-stimulating peptide that can confer protection against toxoplasmosis and provide an important tool for the study of CD4 T cell responses and the design of effective vaccines against the parasite.
Division of Immunology and Pathogenesis, Department of Molecular and Cellular Biology, University of California, Berkeley, California, USA.
Harshita Satija
HS
Grover
Nicolas
N
Blanchard
Federico
F
Gonzalez
Shiao
S
Chan
Ellen A
EA
Robey
Nilabh
N
Shastri
D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation; D000953:Antigens, Protozoan / Q000737:chemistry / Q000276:immunology*; D001921:Brain / Q000469:parasitology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D004195:Disease Models, Animal; D000949:Histocompatibility Antigens Class II / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D059208:Parasite Load; D016052:Protozoan Vaccines / Q000008:administration & dosage / Q000276:immunology; D014122:Toxoplasma / Q000276:immunology* / Q000472:pathogenicity*; D014124:Toxoplasmosis, Animal / Q000276:immunology / Q000469:parasitology / Q000517:prevention & control
D000953:Antigens, Protozoan; D000949:Histocompatibility Antigens Class II; D016052:Protozoan Vaccines