Identification of an antigenic epitope for helper T lymphocytes from carcinoembryonic antigen.
OBJECTIVE
The product of the carcinoembryonic antigen (CEA) gene is an attractive candidate for T-cell-based immunotherapy because it is frequently expressed in epithelial solid carcinomas. Although many CEA peptide epitopes capable of stimulating CTLs have been identified, no MHC class II-restricted T helper epitope has yet been reported.


METHODS
The amino acid sequence of CEA was examined for the presence of potential T helper epitopes, and candidate peptides were used to stimulate in vitro T-cell responses.


RESULTS
We describe here that using an algorithm to identify promiscuous helper T-cell epitopes, a peptide of CEA occupying residue positions 653 to 667 (CEA(653-667)), was effective in inducing in vitro T helper responses in the context of the HLA-DR4, HLA-DR7, and HLA-DR 9 alleles. Most significantly, some of the peptide-reactive helper T lymphocytes were also capable of recognizing naturally processed antigen in the form of recombinant CEA protein or cell lysates from tumors that express CEA. Interestingly, the newly identified helper T-cell epitope was found to overlap with a previously described HLA-A24-restricted CTL epitope, CEA(652-660), which could facilitate the development of a therapeutic vaccine capable of eliciting both CTL and T helper responses in patients suffering from epithelial carcinomas.


CONCLUSIONS
These results indicate that T helper lymphocytes are capable of recognizing CEA as a tumor antigen and that epitope CEA(653-667) could be used for immunotherapy against tumors expressing CEA.
Kobayashi
Hiroya
H
Department of Pathology, Asahikawa Medical College, Asahikawa, Japan.
Omiya
Ryusuke
R
Ruiz
Marta
M
Huarte
Eduardo
E
Sarobe
Pablo
P
Lasarte
Juan José
JJ
Herraiz
Maite
M
Sangro
Bruno
B
Prieto
Jesús
J
Borras-Cuesta
Francisco
F
Celis
Esteban
E
D000465:Algorithms; D000483:Alleles; D017951:Antigen Presentation / Q000276:immunology; D002272:Carcinoembryonic Antigen / Q000276:immunology*; D003110:Colonic Neoplasms / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D018604:Epitope Mapping; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology / Q000378:metabolism; D006684:HLA-DR Antigens / Q000276:immunology; D059810:HLA-DR Serological Subtypes; D015804:HLA-DR4 Antigen / Q000276:immunology; D015809:HLA-DR7 Antigen / Q000276:immunology; D006801:Humans; D016399:Lymphoma, T-Cell / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D014407:Tumor Cells, Cultured
D002272:Carcinoembryonic Antigen; D018984:Epitopes, T-Lymphocyte; D006684:HLA-DR Antigens; D059810:HLA-DR Serological Subtypes; D015804:HLA-DR4 Antigen; D015809:HLA-DR7 Antigen; C038988:HLA-DR9 antigen; D010446:Peptide Fragments; D016178:Granulocyte-Macrophage Colony-Stimulating Factor