Ex-vivo recognition of late-lytic CD8 epitopes specific for Kaposi's sarcoma-associated herpesvirus (KSHV) by HIV/KSHV-coinfected individuals

Viral Immunol. 2011 Jun;24(3):211-20. doi: 10.1089/vim.2010.0133.

Abstract

Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiological agent of Kaposi's sarcoma (KS), the most common cancer in individuals with untreated HIV/AIDS. Host control of KSHV infection and KS oncogenesis by CD8 T cells remains underexplored. Although KSHV CD8 epitopes have been identified, the responses they elicit are weak and little is known about their relative importance. We sought to make a direct comparison of the recognition of a selection of the best-described known epitopes by a cohort of KSHV-seropositive, HIV-co-infected individuals, in order to assess the relative dominance of these epitopes. We further sought to identify novel epitopes from within a candidate immunogenic protein encoded by KSHV ORF28. MHC binding and denaturation assays identified putative novel A*0201-restricted epitopes from within the late-lytic glycoprotein ORF28. Recognition of these candidate epitopes was tested in a cohort of KSHV-seropositive, HIV-1-seropositive, A*0201-positive individuals by ex vivo ELISPOT, and compared with recognition of nine previously described epitopes. One novel late-lytic epitope from ORF28 was recognized by 7.1% of individuals, and was used for further investigation of KSHV-specific T cells using multimer technology. One known late-lytic epitope from the glycoprotein-encoding K8.1 was recognized by 71.4% of individuals, and represented an immunodominant KSHV epitope, but was too hydrophobic for multimer synthesis. This study identifies two KSHV CD8 epitopes derived from late-lytic antigens that are recognized by KSHV-seropositive, HIV co-infected individuals, and will be useful in future immunological studies into the CD8 response against KSHV in similar patient cohorts.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antigens, Viral / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Enzyme-Linked Immunospot Assay
  • Epitope Mapping
  • Epitopes, T-Lymphocyte / immunology*
  • HIV Infections / complications*
  • HIV Infections / immunology
  • Herpesvirus 8, Human / immunology*
  • Humans
  • Male
  • Middle Aged
  • Sarcoma, Kaposi / immunology*
  • Sarcoma, Kaposi / virology
  • T-Lymphocytes, Cytotoxic / immunology*

Substances

  • Antigens, Viral
  • Epitopes, T-Lymphocyte