Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024530 (malaria)
 44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cytotoxic T lymphocytes (CTL) directed against Plasmodium falciparum-derived antigens were shown to play an important role for the protection against malaria. Although several CTL epitopes have been identified from P. falciparum sporozoite-derived antigens, none has been described for the merozoite form. Since the merozoite surface protein (MSP)-1 is a known target of the immune response, we focused on this protein to identify HLA-A*0201-associated epitopes. Using our mass spectrometry-based method [the 'predict-calibrate-detect' (PCD) approach], we were able to identify an MSP-1-derived epitope in the peptide mixture naturally associated with HLA-A*0201 molecules purified from an MSP-1-expressing cell line. CTLs against this epitope were generated from HLA-A*0201 monochain transgenic mice (HHD). They specifically killed MSP-1-expressing HLA-A2-positive target cells. Thus, we describe here the first MHC class I epitope from the merozoite form of P. falciparum. This epitope can be used as a tool for the immunomonitoring of natural or vaccine-induced CTL immune responses against malaria and could eventually be proposed as a component of an anti-malaria peptide-based vaccine.
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PMID:Mass spectrometric identification of an HLA-A*0201 epitope from Plasmodium falciparum MSP-1. 1879 2

Malaria is a severe, life-threatening infectious disease that endangers human health. However, there are no vaccines or immune strategy of vaccines succeeding in both erythrocytic and pre-erythrocytic stage. During the liver stage of the Plasmodium life cycle, sporozoites invade the host liver cells. The sporozoites, then, induce a cellular immune response via the major histocompatibility complex (MHC) molecules on their surfaces. The cytotoxic T lymphocytes (CTLs) then recognize the corresponding antigen-MHC complex on the surfaces of these infected liver cells and kill them. However, dominant epitopes with high MHC affinity are prone to mutation due to immune selection pressure. CTLs evoked by the original dominant epitopes cannot recognize the mutated epitopes, leading to immune evasion. In this study, we have modified the cryptic epitopes of different antigens in the sporozoite and liver stages of Plasmodium falciparum to increase their immunogenicity without changing T cell antigen receptor (TCR)-peptide binding specificity. In addition, we have also added an important erythrocytic phase protective antigen, named apical membrane antigen 1 (AMA-1), to this process with the goal of constructing a complex multi-stage, multi-epitope recombinant DNA vaccine against P. falciparum. The vaccine was tested in HHD-2 mice. The method involved multiple stages of the P. falciparum life cycle as well as elucidation both humoral and cellular immunity. The conclusion drawn from the study was that the vaccine might provide an important theoretical and practical basis for generating effective preventative or therapeutic vaccine against P. falciparum.
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PMID:Analysis of the immune response of a new malaria vaccine based on the modification of cryptic epitopes. 2683 22