Identification of a novel peptide derived from the M-phase phosphoprotein 11 (MPP11) leukemic antigen recognized by human CD8+ cytotoxic T lymphocytes.
OBJECTIVE
There is an urgent need for the development of leukemia-targeted immunotherapeutic approaches using defined leukemia-associated antigens that are preferentially expressed by most leukemia subtypes and absent or minimally expressed in vital tissues. M-phase phosphoprotein 11 protein (MPP11) is extensively overexpressed in leukemic cells and therefore is considered an attractive target for leukemia T cell therapy. We sought to identify potential CD8+ cytotoxic T lymphocytes that specifically recognised peptides derived from the MPP11 antigen.


METHODS
A computer-based epitope prediction program SYFPEITHI, was used to predict peptides from the MPP11 protein that bind to the most common HLA- A*0201 molecule. Peptide binding capacity to the HLA-A*0201 molecule was measured using the T2 TAP-deficient, HLA-A*0201-positive cell line. Dendritic cells were pulsed with peptides and then used to generate CD8+ cytotoxic T lymphocytes (CTL). The CML leukemic cell line K562-A2.1 naturally expressing the MPP11 antigen and engineered to express the HLA-A*0201 molecule was used as the target cell.


RESULTS
We have identified a potential HLA-A*0201 binding epitope (STLCQVEPV) named MPP-4 derived from the MPP11 protein which was used to generate a CTL line. Interestingly, this CTL line specifically recognized peptide-loaded target cells in both ELISPOT and cytotoxic assays. Importantly, this CTL line exerted a cytotoxic effect towards the CML leukemic cell line K562-A2.1.


CONCLUSIONS
This is the first study to describe a novel epitope derived from the MPP11 antigen that has been recognized by human CD8+ CTL.
Tumor Immunology Section, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia.
Ghofran
G
Al Qudaihi
Cynthia
C
Lehe
Anne
A
Dickinson
Khaled
K
Eltayeb
Walid
W
Rasheed
Naeem
N
Chaudhri
Mahmoud
M
Aljurf
Said
S
Dermime
D000951:Antigens, Neoplasm / Q000737:chemistry / Q000276:immunology*; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology; D000939:Epitopes / Q000276:immunology / Q000627:therapeutic use*; D015234:HLA-A Antigens; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D020014:K562 Cells; D007938:Leukemia / Q000188:drug therapy / Q000276:immunology*; D018832:Molecular Chaperones; D015513:Oncogene Proteins / Q000737:chemistry / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology* / Q000627:therapeutic use; D016601:RNA-Binding Proteins; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000951:Antigens, Neoplasm; D004268:DNA-Binding Proteins; C414672:DNAJC2 protein, human; D000939:Epitopes; D015234:HLA-A Antigens; D018832:Molecular Chaperones; D015513:Oncogene Proteins; D010446:Peptide Fragments; D016601:RNA-Binding Proteins