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Identification and Characterization of a T-Helper Peptide from Carcinoembryonic Antigen

¹ Facultad de Medicina y Clínica Universitaria, Fundación para la Investigación Médica Aplicada (FIMA), Universidad de Navarra, Pamplona, Spain, and ² Department of Immunology, Mayo Clinic, Rochester, Minnesota

Purpose: 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.

Experimental Design: 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.

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