Premium
Specific cytotoxic T‐cell immune responses against autoantigens recognized by chronic lymphocytic leukaemia cells
Author(s) -
Zaleska Joanna,
Skorka Katarzyna,
Zajac Malgorzata,
Karczmarczyk Agnieszka,
Karp Marta,
Tomczak Waldemar,
Hus Marek,
Wlasiuk Paulina,
Giannopoulos Krzysztof
Publication year - 2016
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.14098
Subject(s) - cytotoxic t cell , immunology , immune system , biology , cd8 , t cell , antigen , vimentin , cancer research , in vitro , biochemistry , immunohistochemistry
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 ( CFL 1), 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 CFL 1 overexpression and low expression of MYH 9 in comparison with healthy volunteers. We detected specific cytotoxic immune responses for peptides derived from MYHIIA in 66·7%, VIM in 87·5% and CFL 1 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 CFL 1 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 CD 8 + T cells against MYHIIA , VIM and CFL 1 in CLL patients indicates the involvement of antigen‐specific autoreactive T cells in the pathogenesis of CLL .