NATURALLY PROCESSED TISSUE-SPECIFIC AND DIFFERENTIATION STAGE-SPECIFIC AUTOLOGOUS PEPTIDES BOUND BY HLA CLASS-I AND CLASS-II MOLECULES OF CHRONIC MYELOID-LEUKEMIA BLASTS

Structural analysis of naturally processed peptides bound to the HLA c lass I and class II molecules of chronic myeloid leukemia (CML) blast cells was performed to characterize the antigen processing and autoant igen repertoire in this hematopoietic malignancy. Self-peptides derive d from the carboxy-terminal end of the breakpoint cluster region (bcr) protein, as well as several differentiation stage-and tissue-specific self-antigens characteristic of early stages of myeloid differentiati on, such as c-fes, c-pim, granulocyte-macrophage colony-stimulating fa ctor receptor CY chain, proteinase 3, and cathepsin G. were identified . A common characteristic of several of the high copy-number self-pept ides identified in this study is the participation of their parent pro teins in signal transduction or myeloid effector function. Because bcr -abl junctional peptides bind to a limited number of major histocompat ibility complex (MHC) class I alleles, an effective peptide-based immu notherapy strategy for CML requires identification of further tumor-as sociated or tissue-specific peptide antigens binding to common MHC all eles such as HLA-A2. The differentiation stage-and tissue-specific MHC bound peptides found in this study, as well as the naturally processe d proteins from which they are derived, may represent autoantigens tow ards which T-cell responses may potentially be developed for immunothe rapy of hematopoietic malignancies such as CML. (C) 1997 by The Americ an Society of Hematology.