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Specific binding of leukemia oncogene fusion protein peptides to HLA class
I molecules
M Bocchia, PA Wentworth, S Southwood, J Sidney, K McGraw, DA Scheinberg and A Sette
Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Many human leukemias are characterized by chromosomal translocations
yielding hybrid RNAs capable of encoding fusion chimeric proteins. The
unique amino acid sequences found in these oncogenic fusion proteins
represent true tumor-specific antigens that are potentially immunogenic.
Although these leukemia-specific fusion proteins have an intracellular
location, they might be recognized immunologically by T lymphocytes if
peptides derived from the unique sequences are capable of presentation by
the major histocompatibility complex (MHC) molecules on leukemic cells. The
ability of a series of synthetic peptides corresponding to the junctional
sequences of chronic myelogenous leukemia (CML)-derived bcr-abl and acute
promyelocytic leukemia (APL)- derived PML-RAR alpha fusion proteins to bind
to purified class I molecules was studied. A series of 152 peptides 8, 9,
10, and 11 amino acids in length, spanning the b3a2 and b2a2 breakpoints
for CML and PML- RAR alpha A and B breakpoints for APL were analyzed for
HLA A1, A2.1, A3.2, A11, A24, B7, B8, and B27 binding motifs. Twenty-one
CML peptides and 4 APL peptides were predicted to be potential HLA class I
binders. The peptides were tested for binding to appropriate purified HLA
molecules in a competition radioimmunoassay. Four peptides derived from
b3a2 CML breakpoint bound with high (< 50 nmol/L) or intermediate (<
or = 500 nmol/L) affinity to HLA A3, A11, and B8. None of the CML b2a2 or
PML-RAR alpha A or B junctional peptides showed affinity of this magnitude
for the HLA class I molecules tested. This is the first evidence that
tumor-specific breakpoint peptides can bind human MHC class I molecules and
provides a rationale for developing a therapeutic vaccine strategy.
Volume 85,
Issue 10,
pp. 2680-2684,
05/15/1995
Copyright © 1995 by The American Society of Hematology
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