Identification of a MHC class-II restricted epitope in carcinoembryonic antigen.
OBJECTIVE
The carcinoembryonic antigen (CEA) is extensively expressed on the vast majority of colorectal, gastric, and pancreatic carcinomas, and, therefore, is a good target for tumor immunotherapy. CD4+ T-helper (Th) cells play a critical role in initiation, regulation, and maintenance of immune responses. In this study, we sought to identify Th epitopes derived from CEA which can induce CEA-specific Th responses. The combined application with cytotoxic T lymphocyte (CTL) epitopes would be more potent than tumor vaccines that primarily activate CTL alone.


METHODS
We utilized a combined approach of using a computer-based algorithm analysis TEPITOPE and in vitro biological analysis to identify Th epitopes in CEA.


RESULTS
Initial screening of healthy donors showed that all five predicted peptides derived from CEA could induce peptide-specific T-cell proliferation in vitro. We characterized these CEA epitopes by establishing and analyzing peptide-specific T-cell clones. It was shown that CD4+ T-cells specific for the CEA(116 )epitope can recognize and respond to naturally processed CEA protein and CEA(116 )epitope can be promiscuously presented by commonly found major histocompatibility complex (MHC) alleles. Furthermore, it was demonstrated that immunization of human leukocyte antigen (HLA)-DR4 transgenic mice with CEA(116) peptide elicited antigen-specific Th responses which can recognize the antigenic peptides derived from CEA protein and CEA-positive tumors.


CONCLUSIONS
The MHC class II-restricted epitope CEA(116) could be used in the design of peptide-based tumor vaccine against several common cancers expressing CEA.
Shen
Lei
L
Center for Cell and Gene Therapy, Baylor College of Medicine, One Baylor Plaza, Alkek Bldg. N1004, Houston, TX 77030, USA.
Schroers
Roland
R
Hammer
Juergen
J
Huang
Xue F
XF
Chen
Si-Yi
SY
D000465:Algorithms; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D002272:Carcinoembryonic Antigen / Q000276:immunology*; D002455:Cell Division; D003713:Dendritic Cells / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D018604:Epitope Mapping; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology*; D005802:Genes, MHC Class II / Q000276:immunology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology / Q000378:metabolism; D015804:HLA-DR4 Antigen / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007114:Immunization; D007371:Interferon-gamma / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; 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; D015804:HLA-DR4 Antigen; D010446:Peptide Fragments; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor