CMV is associated with immunosenescence and reduced vaccine responses in the elderly (>70 yr). However, the impact of CMV in young adults is less clear. In this study, healthy UK and Senegalese adults aged 18–50 yr (average, 29 yr) were vaccinated with the Ebola vaccine candidate chimpanzee adenovirus type 3–vectored Ebola Zaire vaccine (ChAd3-EBO-Z) and boosted with modified vaccinia Ankara Ebola Zaire–vectored (MVA–EBO-Z) vaccine. CMV carriage was associated with an expansion of phenotypically senescent CD4 + and CD8 + T cells expressing CD57 and killer cell lectin-like receptor G1 (KLRG1), which was negatively associated with vaccine responses in both cohorts. Ebola-specific T cell responses induced by vaccination also contained significantly increased frequencies of terminally differentiated CD57 + KLRG1 + cells in CMV seropositive (CMV + ) individuals. This study suggests that CMV can also affect vaccine responses in younger adults and may have a particularly marked impact in many developing countries where CMV seroprevalence is almost universal.

The nature of the CD8 + T cells that underlie antiviral protective immunological memory in vivo is unclear. We have characterized peptide-specific CD8 + T lymphocytes directly ex vivo from peripheral blood in humans with past exposure to influenza virus, using single cell interferon γ (IFN-γ) release as a measure of effector function. In individuals in the memory state with respect to influenza virus infection, unrestimulated antigen-specific CD8 + T cells displayed IFN-γ release within 6 h of antigen contact, identifying a population of memory CD8 + T cells that exhibit effector function without needing to divide and differentiate over several days. We have quantified circulating CD8 + effector T cells specific for six different MHC class I–restricted influenza virus epitopes. Enumeration of these CD8 + T cells gives frequencies of peptide-specific T cells that correlate with, but are in general severalfold higher than, CTL precursor frequencies derived from limiting dilution analysis, indicating that this novel population of memory CD8 + T cells has hitherto been undetected by standard means. The phenotype of these cells, which persist at a low frequency long after recovery from an acute viral infection, suggests that they play a role in protective immunological memory.

Recombinant HLA-A2, HLA-B8, or HLA-B53 heavy chain produced in Escherichia coli was combined with recombinant β 2 -microglobulin (β 2 m) and a pool of randomly synthesised nonamer peptides. This mixture was allowed to refold to form stable major histocompatability complex (MHC) class I complexes, which were then purified by gel filtration chromatography. The peptides bound to the MHC class I molecules were subsequently eluted and sequenced as a pool. Peptide binding motifs for these three MHC class I molecules were derived and compared with previously described motifs derived from analysis of naturally processed peptides eluted from the surface of cells. This comparison indicated that the peptides bound by the recombinant MHC class I molecules showed a similar motif to naturally processed and presented peptides, with the exception of the peptide COOH terminus. Whereas the motifs derived from naturally processed peptides eluted from HLA-A2 and HLA-B8 indicated a strong preference for hydrophobic amino acids at the COOH terminus, this preference was not observed in our studies. We propose that this difference reflects the effects of processing or transport on the peptide repertoire available for binding to MHC class I molecules in vivo.