Identification of HLA‐B27–restricted cytotoxic T lymphocyte epitope from carcinoembryonic antigen

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...

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Bibliographic Details
Published in:International journal of cancer 2002-01, Vol.97 (1), p.58-63
Main Authors: Huarte, Eduardo, Sarobe, Pablo, Lasarte, Juan José, Brem, Gottfried, Weiss, Elisabeth H., Prieto, Jesús, Borrás‐Cuesta, Francisco
Format: Article
Language:English
Subjects:
Animals
beta 2-Microglobulin - genetics
beta 2-Microglobulin - immunology
Binding Sites
Biological and medical sciences
carcinoembryonic antigen
Carcinoembryonic Antigen - genetics
Carcinoembryonic Antigen - immunology
Cell Line
Cross Reactions
cytotoxic T lymphocyte
Epitopes, T-Lymphocyte - immunology
HLA-B27 Antigen - immunology
HLA‐B27
Host-tumor relations. Immunology. Biological markers
Humans
Immunization
Interferon-gamma - metabolism
Medical sciences
Mice
Mice, Transgenic
peptides
Peptides - chemistry
Peptides - immunology
T-Lymphocytes, Cytotoxic - immunology
tumor
Tumors
Vaccinia virus
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Summary: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.
ISSN:0020-7136
1097-0215
DOI:10.1002/ijc.1579