A novel α-fetoprotein-derived helper T-lymphocyte epitope with strong immunogenicity in patients with hepatocellular carcinoma.

Scientific Reports
Toshikatsu TamaiShuichi Kaneko

Abstract

α-Fetoprotein (AFP) is considered a good target for immunotherapy strategies against hepatocellular carcinoma (HCC); however, no immunodominant AFP-derived MHC class II-restricted helper T-lymphocyte (HTL) epitope has been reported. Therefore, we identified novel AFP-derived HTL epitopes possessing high immunogenicity. HTL epitopes were predicted using the online service, and peptides were subsequently synthesized. Four newly synthesized peptides showed positive reactivity in >20% patients on ELISPOT using peripheral blood mononuclear cells (PBMCs). Among these, the highest rate was shown by AFP1 (MKWVESIFLIFLLNFTESRT), which also showed the highest positive rate in cell proliferation assays. Binding assays demonstrated that AFP1 had strong binding properties toward MHC molecules. Further, blocking assays performed using an anti-HLA-DR antibody showed that immune response decreased, confirming the binding of AFP1 to HLA-DR molecules. Furthermore, the survival rates of patients with stages II-IV HCC indicated that T cell response against AFP1 led to significantly greater survival that of patients without T cell response. When evaluating immune response against AFP1 before and after HCC treatment, an increase in the frequency of ...Continue Reading

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Datasets Mentioned

BETA
AAB58754

Methods Mentioned

BETA
PCR
flow cytometry

Key Resources (RRID) Mentioned

CVCL_T098
CVCL_T166

Software Mentioned

TEPITOPE
ProPred

Related Concepts

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