Immunodominant West Nile Virus T Cell Epitopes Are Fewer in Number and Fashionably Late

J Immunol. 2016 May 15;196(10):4263-73. doi: 10.4049/jimmunol.1501821. Epub 2016 Apr 20.

Abstract

Class I HLA molecules mark infected cells for immune targeting by presenting pathogen-encoded peptides on the cell surface. Characterization of viral peptides unique to infected cells is important for understanding CD8(+) T cell responses and for the development of T cell-based immunotherapies. Having previously reported a series of West Nile virus (WNV) epitopes that are naturally presented by HLA-A*02:01, in this study we generated TCR mimic (TCRm) mAbs to three of these peptide/HLA complexes-the immunodominant SVG9 (E protein), the subdominant SLF9 (NS4B protein), and the immunorecessive YTM9 (NS3 protein)-and used these TCRm mAbs to stain WNV-infected cell lines and primary APCs. TCRm staining of WNV-infected cells demonstrated that the immunorecessive YTM9 appeared several hours earlier and at 5- to 10-fold greater density than the more immunogenic SLF9 and SVG9 ligands, respectively. Moreover, staining following inhibition of the TAP demonstrated that all three viral ligands were presented in a TAP-dependent manner despite originating from different cellular compartments. To our knowledge, this study represents the first use of TCRm mAbs to define the kinetics and magnitude of HLA presentation for a series of epitopes encoded by one virus, and the results depict a pattern whereby individual epitopes differ considerably in abundance and availability. The observations that immunodominant ligands can be found at lower levels and at later time points after infection suggest that a reevaluation of the factors that combine to shape T cell reactivity may be warranted.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology
  • Antibody Specificity
  • Antigen Presentation*
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Line, Tumor
  • Dendritic Cells / virology
  • Epitopes, T-Lymphocyte / immunology*
  • Female
  • HLA-A Antigens / immunology
  • Humans
  • Immunodominant Epitopes / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Receptors, Antigen, T-Cell / immunology
  • West Nile virus / immunology*

Substances

  • Antibodies, Monoclonal
  • Epitopes, T-Lymphocyte
  • HLA-A Antigens
  • Immunodominant Epitopes
  • Receptors, Antigen, T-Cell