Flow cytometric analysis of peptide binding to major histocampatibility complex class I for hepatitis C virus core T-cell epitopes

Cytometry. 2000 Dec 1;41(4):271-8. doi: 10.1002/1097-0320(20001201)41:4<271::aid-cyto5>3.0.co;2-m.

Abstract

Background/methods: To characterize the repertoire of T-cell epitopes on the hepatitis C virus (HCV) core protein, we studied major histocompatibility complex (MHC) class I binding of 75 decapeptides on 20 human B-cell lines and murine spleen cells using a flow cytometric assay. The results were compared with MHC class I stabilization on T2 cells, the SYFPEITHI algorithm, and known T-cell epitopes from the literature.

Results: Binding of peptides proved to be specific for MHC class I molecules. We observed peak fluorescence signals at positions amino acids (aa) 35-44, aa 87-96, aa 131-140, and aa 167-176 in virtually all HLA-A2-positive cell lines. These sites corresponded to T-cell epitopes predicted by SYFPEITHI and the positions of known T-cell epitopes, whereas T2 stabilization was at variance for two peptides. The assay was applied to HLA-A2-negative cells and murine spleen cells without further modification, and identified additional peptides, corresponding to known T-cell epitopes.

Conclusions: Peptide binding to different MHC class I alleles can be mapped rapidly by a flow cytometric assay and enables a first orientation on the sites of possible T-cell epitopes. Application of this assay to HCV core suggests a rather limited repertoire of epitopes in the Caucasoid population.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / immunology
  • Binding, Competitive
  • Biotinylation
  • Cells, Cultured
  • Epitope Mapping / methods*
  • Epitopes, T-Lymphocyte / immunology
  • Epitopes, T-Lymphocyte / metabolism*
  • Flow Cytometry / methods*
  • Fluorescent Dyes
  • Histocompatibility Antigens Class I / immunology
  • Histocompatibility Antigens Class I / metabolism*
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Oligopeptides / immunology
  • Oligopeptides / metabolism
  • Protein Binding
  • Spleen / immunology
  • T-Lymphocytes, Cytotoxic / immunology
  • T-Lymphocytes, Cytotoxic / metabolism
  • Viral Core Proteins / immunology*
  • Viral Core Proteins / metabolism*

Substances

  • Epitopes, T-Lymphocyte
  • Fluorescent Dyes
  • Histocompatibility Antigens Class I
  • Oligopeptides
  • Viral Core Proteins
  • nucleocapsid protein, Hepatitis C virus