CTLs specific for bcr-abl joining region segment peptides fail to lyse leukemia cells expressing p210 bcr-abl protein.
The aim of the current study was to determine whether immunization with synthetic peptides corresponding to the joining region segment of p210 bcr-abl chimeric protein can elicit CD8+ cytotoxic T lymphocytes (CTLs) capable of specifically lysing leukemia cells. BALB/c mice were immunized with peptides identical to the joining region segment of p210 bcr-abl protein. Class I major histocompatibility complex (MHC)-restricted bcr-abl peptide-specific CD8+ CTLs were elicited. The CTL clones were H-2 Kd restricted and specifically recognized a nonamer peptide of the combined sequence of bcr-abl amino acids but neither bcr nor abl amino acid sequence alone. Despite specificity and substantial lytic potential against syngeneic cell line incubated with exogenously supplied peptides, the bcr-abl peptide-specific CTLs failed to lyse syngeneic murine leukemia cells expressing human p210 bcr-abl protein containing the same bcr-abl joining region peptide sequence. Similarly, the bcr-abl peptide-specific CTLs did not lyse human bcr-abl-positive chronic myelogenous leukemia cells expressing murine class I MHC antigen (i.e., K562 cells infected with vaccinia virus expressing H-2 Kd). The appropriateness of the joining region segment of bcr-abl protein to serve as a T cell target depends upon whether that segment is presented by class I MHC in a concentration high enough to stimulate CTLs. The current experiments using murine peptide-specific CTLs could not establish that the joining region of bcr-abl protein is processed and presented by class I MHC antigen-processing pathway, but the possibility was not ruled out. Alternative models and/or strategies are necessary.
Department of Medicine, University of Washington, Seattle, USA.
W
W
Chen
H
H
Qin
V A
VA
Reese
M A
MA
Cheever
D000595:Amino Acid Sequence; D000818:Animals; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000276:immunology*; D006183:H-2 Antigens / Q000502:physiology; D006801:Humans; D007114:Immunization; D007938:Leukemia / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured
D006183:H-2 Antigens; C024755:H-2K(K) antigen; D016044:Fusion Proteins, bcr-abl