Identification and characterization of a T-helper peptide from carcinoembryonic antigen.
OBJECTIVE
The purpose of this research was to identify promiscuous T-helper cell determinants (THd) from carcinoembryonic antigen (CEA) to be used to prime T-cell help for cancer therapy. CEA was selected because this antigen is expressed in an important variety of carcinomas.


METHODS
Potential promiscuous THd from CEA were predicted using available computer algorithms. Predicted peptides were synthesized and tested in binding experiments to different HLA-DR molecules. Binder peptides were then used to prime T-cell responses both in vitro and in vivo.


RESULTS
Twenty 15-mer peptides from CEA were predicted to bind to different HLA-DR molecules. The promiscuous character of these peptides was demonstrated in binding experiments. Fifteen of 20 peptides tested were able to bind to HLA-DR4, but only CEA (625-639) was shown to be presented after processing of recombinant CEA. CEA (625-639) was also found to be presented by HLA-DR53. Moreover, immunization of HLA-DR4 transgenic mice with CEA (625-639) in conjunction with class I epitope OVA (257-264), induced a CTL response specific of OVA (257-264).


CONCLUSIONS
CEA (625-639) might be a relevant promiscuous THd peptide for cancer therapy.
Ruiz
Marta
M
Facultad de Medicina y Clínica Universitaria, Fundación para la Investigación Médica Aplicada , Universidad de Navarra, Pamplona, Spain.
Kobayashi
Hiroya
H
Lasarte
Juan José
JJ
Prieto
Jesús
J
Borrás-Cuesta
Francisco
F
Celis
Esteban
E
Sarobe
Pablo
P
D000465:Algorithms; D000818:Animals; D000941:Antigens / Q000737:chemistry; D002272:Carcinoembryonic Antigen / Q000737:chemistry* / Q000276:immunology*; D002277:Carcinoma / Q000378:metabolism; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D000939:Epitopes / Q000737:chemistry; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006684:HLA-DR Antigens / Q000737:chemistry; D059845:HLA-DRB4 Chains; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010455:Peptides / Q000737:chemistry*; D011485:Protein Binding; D011994:Recombinant Proteins / Q000737:chemistry; D013601:T-Lymphocytes / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000737:chemistry*
D000941:Antigens; D002272:Carcinoembryonic Antigen; D000939:Epitopes; D006684:HLA-DR Antigens; C050610:HLA-DR53; D059845:HLA-DRB4 Chains; D010455:Peptides; D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor