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Identification of HLA‐B27–restricted cytotoxic T lymphocyte epitope from carcinoembryonic antigen
Author(s) -
Huarte Eduardo,
Sarobe Pablo,
Lasarte Juan José,
Brem Gottfried,
Weiss Elisabeth H.,
Prieto Jesús,
BorrásCuesta Francisco
Publication year - 2001
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.1579
Subject(s) - epitope , carcinoembryonic antigen , cytotoxic t cell , ctl* , antigen , immunology , virology , human leukocyte antigen , major histocompatibility complex , cd8 , biology , microbiology and biotechnology , chemistry , cancer , in vitro , biochemistry , genetics
Characterization of epitopes recognized by cytotoxic T lymphocytes (CTLs) in the sequence of tumor antigens is an important step in the development of tumor therapies. Because carcinoembryonic antigen (CEA) is a protein expressed in a high number of epithelial tumors, it is an interesting target to study. We screened for the presence of HLA‐B27–restricted CTL epitopes from CEA by studying the binding to HLA‐B27 of 31 synthetic peptides predicted to bind to this molecule. This afforded 16 peptides with moderate or high binding affinity. Immunization of HLA‐B27 transgenic mice with the best binder peptides yielded 4 immunogenic peptides: CEA(9–17), CEA(9–18), CEA(138–146) and CEA(360–369). However, splenocytes from mice immunized with a vaccinia virus–expressing CEA recognized only CEA(9–18). These CTLs were of the CD8 + phenotype, which upon stimulation with peptide specifically produced IFN‐γ. Moreover, they did not cross‐react against peptides of region 9–18 from proteins of the CEA family. Our results show that CEA(9–18) may induce specific CTL responses against CEA. © 2002 Wiley‐Liss, Inc.