Definition of T cell epitopes within the 19 kDa carboxylterminal fragment of Plasmodium yoelii merozoite surface protein 1 (MSP1(19)) and their role in immunity to malaria.
MSP1(19) is one of the leading malaria vaccine candidates. However, the mechanism of protection is not clear. To determine whether MSP1(19)-specific effector T cells can control parasitaemia, we analysed the specificity of T cells induced following immunization with recombinant forms of P. yoelii MSP1(19) and asked whether they could protect mice. There was no evidence that effector T cells were capable of protecting since: (1) immunization of mice with yMSP1(19), but not defined epitopes, was able to induce protection; and (2) long term MSP1(19)-specific CD4+ T cell lines were incapable of adoptively transferring protection. In contrast, priming mice with the T cell epitopes resulted in a rapid anamnestic antibody response to MSP1(19) after either challenge with MSP1(19) or parasite. Thus, MSP1(19) contains multiple T cell epitopes but such epitopes are the targets of helper T cells for antibody response but not of identified effector T cells capable of controlling parasitaemia.
Tian
J H
JH
Laboratory of Parasitic Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Good
M F
MF
Hirunpetcharat
C
C
Kumar
S
S
Ling
I T
IT
Jackson
D
D
Cooper
J
J
Lukszo
J
J
Coligan
J
J
Ahlers
J
J
Saul
A
A
Berzofsky
J A
JA
Holder
A A
AA
Miller
L H
LH
Kaslow
D C
DC
D019264:Adoptive Transfer; D000595:Amino Acid Sequence; D000818:Animals; D000953:Antigens, Protozoan / Q000737:chemistry / Q000276:immunology*; D000954:Antigens, Surface / Q000737:chemistry / Q000276:immunology; D002460:Cell Line; D018604:Epitope Mapping; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry / Q000276:immunology*; D005260:Female; D008213:Lymphocyte Activation; D008288:Malaria / Q000276:immunology*; D017780:Malaria Vaccines / Q000737:chemistry / Q000276:immunology*; D020066:Merozoite Surface Protein 1; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D008969:Molecular Sequence Data; D010967:Plasmodium yoelii / Q000276:immunology*; D011498:Protein Precursors / Q000737:chemistry / Q000276:immunology*; D015800:Protozoan Proteins / Q000737:chemistry / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
D000953:Antigens, Protozoan; D000954:Antigens, Surface; D018984:Epitopes, T-Lymphocyte; D017780:Malaria Vaccines; D020066:Merozoite Surface Protein 1; D011498:Protein Precursors; D015800:Protozoan Proteins