Epitope analysis of human T-cell response to MSP-1 of Plasmodium falciparum in malaria-nonexposed individuals.
BACKGROUND
MSP-1 of Plasmodium falciparum induces strong proliferative T cell responses even in malaria-nonexposed individuals. Epitopes recognized by malaria-nonimmune T cells have not been identified, and immunological mechanisms inducing such T cell responses remain to be uncovered. MSP-1 is a vaccine candidate, and it should be understood whether those epitopes have any roles in MSP-1-mediated protective immunity. The T epitopes-inducing malaria-naive T cell response was analyzed in the hope of understanding the underlying mechanisms.


METHODS
Human T cell lines and clones reactive to MSP-1 of P. falciparum were established from malaria-nonexposed Japanese donors in vitro, and epitope peptides were identified. Sequences of those epitope peptides were compared to unrelated peptides in the data base. One of those peptides was tested for both binding to HLA-DR molecules and inducing proliferative responses of MSP-1-reactive T cells.


RESULTS
There are at least 6 epitopes recognized by malaria-naive T cells under the restriction by HLA-DRB1*1502 or 0802. Important amino acids for the T cell recognition were identified for an MSP-1 peptide. A yeast peptide which shared those residues induced proliferative responses of MSP-1-reactive T cells.


CONCLUSIONS
We identified T epitopes in the N-terminal region of MSP-1, some of which showed molecular similarities with unrelated environmental antigens, suggesting the presence of cross-reactive T epitopes in MSP-1. Cytokine production in response to those epitopes suggests regulatory functions of those T cells during primary infection with P. falciparum.
Ohta
N
N
Department of Medical Zoology, Nagoya City University Medical School, Nagoya, Japan. nohta@med.nagoya-cu.ac.jp
Iwaki
K
K
Itoh
M
M
Fu
J
J
Nakashima
S
S
Hato
M
M
Tolle
R
R
Bujard
H
H
Saitoh
A
A
Tanabe
K
K
D000595:Amino Acid Sequence; D000818:Animals; D000953:Antigens, Protozoan / Q000235:genetics; D002460:Cell Line; D003429:Cross Reactions; D000939:Epitopes / Q000235:genetics; D006684:HLA-DR Antigens / Q000235:genetics; D006801:Humans; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D016778:Malaria, Falciparum / Q000276:immunology*; D020066:Merozoite Surface Protein 1; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology; D010963:Plasmodium falciparum / Q000235:genetics / Q000276:immunology*; D011498:Protein Precursors / Q000235:genetics / Q000276:immunology*; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology*; D017386:Sequence Homology, Amino Acid; D013601:T-Lymphocytes / Q000276:immunology*
D000953:Antigens, Protozoan; D000939:Epitopes; D006684:HLA-DR Antigens; D020066:Merozoite Surface Protein 1; D010446:Peptide Fragments; D011498:Protein Precursors; D015800:Protozoan Proteins