An Hsp70 peptide initiates NK cell killing of leukemic blasts after stem cell transplantation.
In contrast to solid tumors, leukemic blasts frequently present both Hsp70 and HLA-E on their cell surface and thereby present activating and inhibitory signals to CD94(+) NK cells. In the first 12 months after stem cell transplantation (SCT) CD94(+) NK cells clearly dominate over CD3(+)/CD16(-)/56(-) T and CD3(+)/CD16(+)/56(+) NK-like T cells. An incubation of post-SCT-derived peripheral blood lymphocytes with the Hsp70 peptide TKD and IL-15 enhances the cell surface density of CD56/CD94 and initiates the cytolytic activity of NK cells against Hsp70/HLA-E double-positive autologous and allogeneic leukemic blasts. Hsp70 was identified as the target structure for TKD-activated NK cells.
Gross
Catharina
C
National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, USA.
Holler
Ernst
E
Stangl
Stefan
S
Dickinson
Anne
A
Pockley
A Graham
AG
Asea
Alexzander A
AA
Mallappa
Nagaraja
N
Multhoff
Gabriele
G
D015703:Antigens, CD / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006680:HLA Antigens / Q000502:physiology; D018840:HSP70 Heat-Shock Proteins / Q000502:physiology*; D015395:Histocompatibility Antigens Class I / Q000502:physiology; D006801:Humans; D019409:Interleukin-15 / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology*; D007938:Leukemia / Q000276:immunology / Q000473:pathology*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology / Q000473:pathology; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000276:immunology / Q000473:pathology; D015470:Leukemia, Myeloid, Acute / Q000276:immunology / Q000473:pathology; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008875:Middle Aged; D010446:Peptide Fragments / Q000502:physiology*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000276:immunology / Q000473:pathology; D033581:Stem Cell Transplantation; D014407:Tumor Cells, Cultured; D000097625:HLA-E Antigens
D015703:Antigens, CD; D006680:HLA Antigens; D018840:HSP70 Heat-Shock Proteins; D015395:Histocompatibility Antigens Class I; D019409:Interleukin-15; D010446:Peptide Fragments; D000097625:HLA-E Antigens