Human CD4 lymphocytes specifically recognize a peptide representing the fusion region of the hybrid protein pml/RAR alpha present in acute promyelocytic leukemia cells.
Fusion proteins present in leukemic cells frequently contain a new amino acid at the fusion point. We tested whether a peptide (BCR1/25) encompassing the fusion region of the hybrid molecule pml/RAR alpha, which is selectively expressed by acute promyelocytic leukemia (APL) cells, can be recognized by human T lymphocytes in vitro. CD4+ lymphocytes, at both polyclonal and clonal level, recognized peptide BCR1/25 in an HLA-DR--restricted fashion on presentation by autologous antigen-presenting cell (APC) or by APC expressing the HLA-DR11 restricting molecule. Control peptides corresponding to the normal pml and RAR alpha proteins were not recognized. One clone (DEG5) also exerted a high and specific cytotoxicity against autologous cells pulsed with BCR1/25. The autologous DE LCL containing a transduced pml/RAR alpha fusion gene and expressing a bcr1 type of the pml/RAR alpha hybrid protein induced the proliferation of DE anti-BCR1/25 T cell clones. It is concluded that the bcr1 type-pml/RAR alpha fusion protein of APL contains an antigenic site, absent from the normal parent molecules and recognized by human CD4+ lymphocytes.
Gambacorti-Passerini
C
C
Division of Experimental Oncology D, Istituto Nazionale Tumori, Milan, Italy.
Grignani
F
F
Arienti
F
F
Pandolfi
P P
PP
Pelicci
P G
PG
Parmiani
G
G
D000595:Amino Acid Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002352:Carrier Proteins / Q000032:analysis / Q000276:immunology*; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D006684:HLA-DR Antigens / Q000032:analysis / Q000235:genetics; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000032:analysis / Q000276:immunology*; D009687:Nuclear Proteins; D015514:Oncogene Proteins, Fusion; D000071156:Promyelocytic Leukemia Protein; D018168:Receptors, Retinoic Acid; D011993:Recombinant Fusion Proteins / Q000032:analysis / Q000276:immunology*; D014157:Transcription Factors / Q000032:analysis / Q000276:immunology*; D025521:Tumor Suppressor Proteins
D002352:Carrier Proteins; D006684:HLA-DR Antigens; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D015514:Oncogene Proteins, Fusion; D000071156:Promyelocytic Leukemia Protein; D018168:Receptors, Retinoic Acid; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C093476:promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein; C070576:PML protein, human