Persistent CD8 T Cell Marks Caused by the HCMV Infection in Seropositive Adults: Prevalence of HLA-E-Reactive CD8 T Cells

Cells. 2023 Mar 14;12(6):889. doi: 10.3390/cells12060889.

Abstract

This study investigated the frequency and peptide specificity of long-lasting HCMV-specific CD8 T cells in a cohort of 120 cytomegalovirus seropositive (HCMV+) healthy carriers with the aim of deciphering the relative contribution of unconventional HLA-E- versus conventional HLA-A2-specific CD8 T cells to long-term T cell memory expansion in HCMV immunity. The presence of HCMV-specific CD8 T cells was investigated by flow cytometry using five MHC/peptide tetramer complexes (HLA-A2/pp65, HLA-A2/IE1 and three different HLA-E/UL40). Here, we report that 50% of HCMV+ healthy individuals possess HCMV-specific CD8 T cells, representing ≥0.1% of total blood CD8 T cells years post-infection. Around a third (30.8%) of individuals possess HLA-A2-restricted (A2pp65 or A2IE1) and an equal proportion (27.5%) possess an HLA-E/UL40 CD8 T response. Concomitant HLA-E- and HLA-A2-reactive CD8 T cells were frequently found, and VMAPRTLIL peptide was the major target. The frequency of HLA-E/VMAPRTLIL among total blood CD8 T cells was significantly higher than the frequency of HLA-A2pp65 T cells (mean values: 5.9% versus 2.3%, p = 0.0354). HLA-EUL40 CD8 T cells display lower TCR avidity but similar levels of CD3 and CD8 coreceptors. In conclusion, HLA-E-restricted CD8 T cells against the VMAPRTLIL UL40 peptide constitute a predominant subset among long-lasting anti-HCMV CD8 T cells.

Keywords: CD8 T cells; HCMV immunity; HCMV infection; HLA-E; UL40.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • CD8-Positive T-Lymphocytes
  • Cytomegalovirus Infections*
  • HLA-A2 Antigen
  • HLA-E Antigens
  • Humans
  • Immediate-Early Proteins*
  • Peptides
  • Prevalence
  • Viral Proteins

Substances

  • HLA-A2 Antigen
  • Viral Proteins
  • Immediate-Early Proteins
  • Peptides

Grants and funding

This research was funded by the «Association Grégory Lemarchal» and «Vaincre la Mucoviscidose» (France), grant number RF20190502487 and by l’Institut de Recherche en Santé Respiratoire des Pays de la Loire (France), grant number LSC 10280 and by the ANR grant number 17-RHUS-0010 Kidney Transplantation Diagnostics Innovation (KTD Innov).