Direct evidence that leukemic cells present HLA-associated immunogenic peptides derived from the BCR-ABL b3a2 fusion protein.
The BCR-ABL oncogene is central in the pathogenesis of chronic myeloid leukemia (CML). Here, tandem nanospray mass spectrometry was used to demonstrate cell surface HLA-associated expression of the BCR-ABL peptide KQSSKALQR on class I-negative CML cells transfected with HLA-A*0301, and on primary CML cells from HLA-A3-positive patients. These patients mounted a cytotoxic T-lymphocyte response to KQSSKALQR that also killed autologous CML cells, and tetramer staining demonstrated the presence of circulating KQSSKALQR-specific T cells. The findings are the first demonstration that CML cells express HLA-associated leukemia-specific immunogenic peptides and provide a sound basis for immunization studies against BCR-ABL.
Clark
R E
RE
Department of Life Sciences and Chemistry and Physics, Nottingham Trent University, Nottingham, United Kingdom.
Dodi
I A
IA
Hill
S C
SC
Lill
J R
JR
Aubert
G
G
Macintyre
A R
AR
Rojas
J
J
Bourdon
A
A
Bonner
P L
PL
Wang
L
L
Christmas
S E
SE
Travers
P J
PJ
Creaser
C S
CS
Rees
R C
RC
Madrigal
J A
JA
D000328:Adult; D000595:Amino Acid Sequence; D017951:Antigen Presentation; D000951:Antigens, Neoplasm / Q000737:chemistry / Q000276:immunology*; D000954:Antigens, Surface / Q000737:chemistry / Q000276:immunology*; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000737:chemistry / Q000276:immunology*; D015791:HLA-A3 Antigen / Q000235:genetics / Q000276:immunology*; D006801:Humans; D020014:K562 Cells / Q000276:immunology; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000737:chemistry / Q000276:immunology*; D014411:Neoplastic Stem Cells / Q000276:immunology*; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000276:immunology; D021241:Spectrometry, Mass, Electrospray Ionization; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014162:Transfection
D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D015791:HLA-A3 Antigen; D009363:Neoplasm Proteins; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; D016044:Fusion Proteins, bcr-abl