Specific cytotoxic T-cell immune responses against autoantigens recognized by chronic lymphocytic leukaemia cells.
Mounting evidence suggests that autoreactivity and inflammatory processes are involved in the pathogenesis of chronic lymphocytic leukaemia (CLL). Cytoskeletal proteins, including non-muscle myosin heavy chain IIA (MYHIIA), vimentin (VIM) and cofilin-1 (CFL1), exposed on the surface of apoptotic cells have been identified as autoantigens that are recognized by the specific B-cell receptors of the CLL cells. In 212 CLL patients analysed with quantitative reverse transcriptase-polymerase chain reaction we found CFL1 overexpression and low expression of MYH9 in comparison with healthy volunteers. We detected specific cytotoxic immune responses for peptides derived from MYHIIA in 66·7%, VIM in 87·5% and CFL1 in 62·5% CLL patients in an Enzyme-Linked ImmunoSpot assay. Low frequencies of autoreactive peptide-specific T cells were detected against MYHIIA, VIM and CFL1 in CLL patients ex vivo; most of the detected cells had an effector-memory phenotype. Our findings support the existence of cytotoxic immune responses against three autoantigens that have been identified as targets of CLL clonotypic B-cell receptors. The presence of autoreactive CD8(+) T cells against MYHIIA, VIM and CFL1 in CLL patients indicates the involvement of antigen-specific autoreactive T cells in the pathogenesis of CLL.
Department of Experimental Haemato-oncology, Medical University of Lublin, Lublin, Poland.
Joanna
J
Zaleska
Department of Experimental Haemato-oncology, Medical University of Lublin, Lublin, Poland.
Katarzyna
K
Skorka
Department of Experimental Haemato-oncology, Medical University of Lublin, Lublin, Poland.
Malgorzata
M
Zajac
Department of Experimental Haemato-oncology, Medical University of Lublin, Lublin, Poland.
Agnieszka
A
Karczmarczyk
Department of Experimental Haemato-oncology, Medical University of Lublin, Lublin, Poland.|Postgraduate School of Molecular Medicine, Warsaw, Poland.
Marta
M
Karp
Department of Haemato-oncology and Bone Marrow Transplantation, Medical University of Lublin, Lublin, Poland.
Waldemar
W
Tomczak
Department of Haemato-oncology and Bone Marrow Transplantation, Medical University of Lublin, Lublin, Poland.
Marek
M
Hus
Department of Experimental Haemato-oncology, Medical University of Lublin, Lublin, Poland.
Paulina
P
Wlasiuk
Department of Experimental Haemato-oncology, Medical University of Lublin, Lublin, Poland.|Department of Haematology, St. John's Cancer Centre, Lublin, Poland.
Krzysztof
K
Giannopoulos
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001324:Autoantigens / Q000276:immunology*; D051338:Cofilin 1 / Q000276:immunology; D005260:Female; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D018995:Myosin Heavy Chains / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014746:Vimentin / Q000276:immunology
D001324:Autoantigens; C495810:CFL1 protein, human; D051338:Cofilin 1; D014746:Vimentin; D018995:Myosin Heavy Chains
antigen stimulation; chronic lymphocytic leukaemia; cofilin-1; non-muscle myosin heavy chain IIA; vimentin