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Fetoprotein1
*
Divisions of Surgical Oncology,
Hematology/Oncology,
Pasarow Mass Spectrometry Laboratory, Department of Chemistry and Biochemistry, and Psychiatry and Neuropsychiatric Institute,
Experimental Radiation Oncology,
¶ and the Department of Microbiology, Immunology and Molecular Genetics, University of California Los Angeles Medical Center, Los Angeles, CA 90095
fetoprotein (AFP)-derived peptide epitopes can be recognized by
human T cells in the context of MHC class I. We determined the identity
of AFP-derived peptides, presented in the context of HLA-A*0201, that
could be recognized by the human (h) T cell repertoire. We screened 74
peptides and identified 3 new AFP epitopes, hAFP137–145,
hAFP158–166, and hAFP325–334, in addition to
the previously reported hAFP542–550. Each possesses two
anchor residues and stabilized HLA-A*0201 on T2 cells in a
concentration-dependent class I binding assay. The peptides were stable
for 2–4 h in an off-kinetics assay. Each peptide induced
peptide-specific T cells in vitro from several normal HLA-A*0201
donors. Importantly, these hAFP peptide-specific T cells also were
capable of recognizing HLA-A*0201+/AFP+ tumor
cells in both cytotoxicity assays and IFN-
enzyme-linked immunospot
assays. The immunogenicity of each peptide was tested in vivo with
HLA-A*0201/Kb-transgenic mice. After immunization with each
peptide emulsified in CFA, draining lymph node cells produced IFN-
on recognition of cells stably transfected with hAFP. Furthermore, AFP
peptide-specific T cells could be identified in the spleens of mice
immunized with dendritic cells transduced with an AFP-expressing
adenovirus (AdVhAFP). Three of four AFP peptides could be identified by
mass spectrometric analysis of surface peptides from an HLA-A*0201
human hepatocellular carcinoma (HCC) cell line. Thus, compelling
immunological and physiochemical evidence is presented that at least
four hAFP-derived epitopes are naturally processed and presented in the
context of class I, are immunogenic, and represent potential targets
for hepatocellular carcinoma immunotherapy.
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