HLA class I-restricted T cell epitopes of the kinetoplastid membrane protein-11 presented by Leishmania donovani-infected human macrophages.
Visceral leishmaniasis is a protozoal disease caused by the intracellular parasites Leishmania donovani and L. chagasi/infantum, and it is usually deadly if not treated. To date, no vaccine exists for prophylaxis or immunotherapy, nor has it been established which effector mechanisms of the immune system are most instrumental against the parasites. Recent reports have suggested that CD8(+) T cells, in addition to CD4(+) T cells, might play major roles in the defense against infection and in the cure of the disease. To identify epitopes recognized by CD8(+) T cells that can be used for immune monitoring to investigate the role of these cells in human visceral leishmaniasis, as well as in vaccine development, we scanned the entire sequence of the leishmanial protein kinetoplastid membrane protein (kmp)-11 with overlapping nonapeptides. Thirty peptides that specifically trigger interferon- gamma secretion by human CD8(+) T cells were identified. Four T cell lines with specificities for different peptides recognize Leishmania-infected autologous macrophages, which proves that kmp-11 is processed and presented via the major histocompatibility complex class I pathway of infected cells. Kmp-11 is thus a candidate antigen for the development of T cell vaccines.
Basu
Rajatava
R
Clinical Research Group, Department of Dermatology, Venerology and Allergology, Charite-Universitatsmedizin Berlin, Humboldt University, Berlin, D-10117, Germany.
Roy
Syamal
S
Walden
Peter
P
D000595:Amino Acid Sequence; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000469:parasitology; D018984:Epitopes, T-Lymphocyte / Q000502:physiology; D006680:HLA Antigens / Q000502:physiology*; D006801:Humans; D007893:Leishmania donovani / Q000276:immunology*; D007898:Leishmaniasis, Visceral / Q000276:immunology* / Q000469:parasitology*; D008264:Macrophages / Q000276:immunology; D008562:Membrane Glycoproteins / Q000235:genetics*; D008969:Molecular Sequence Data; D015800:Protozoan Proteins / Q000235:genetics*
D018984:Epitopes, T-Lymphocyte; D006680:HLA Antigens; D008562:Membrane Glycoproteins; D015800:Protozoan Proteins; C090009:kinetoplastid membrane protein 11, Leishmania donovani