Comparative Analysis of CD81 T Cell Responses against Human Cytomegalovirus Proteins pp65 and Immediate Early 1 Shows Similarities in Precursor Frequency, Oligoclonality, and Phenotype

CD8þ T cells are key effectors of the immune response against human cytomegalovirus (HCMV). A number of HCMV-derived CD8þ T cell epitopes are known. Using epitope prediction and subsequent testing for interferon-g responses by the ELISPOT assay, we identified an opti-mal human leukocyte antigen (HLA) – A*0201–restricted CD8þ T cell epitope derived from the major immediate early 1 (IE-1) gene product. As many as one-third of HLA-A*0201 – positive, HCMV-seropositive donors make responses to this peptide (residues 316–324 [VLEETSVML]), which can exceed responses against a published immunodominant pp65 epitope (residues 495– 503 [NLVPMVATV]). Major histocompatibility complex peptide tetramer staining facilitated detailed phenotypic analyses and revealed populations that resemble terminally differentiated effector cells (CD57þ and CD282), with considerable restriction in T cell receptor b-chain vari-able region use. The results confirm that, although pp65 is a major target for CD8þ T cells, the IE-1 protein may itself stimulate comparable responses in some persons. Human cytomegalovirus (HCMV) is a widespread betaher-pesvirus that infects 60%–90 % of the population worldwide. Primary infection is largely asymptomatic and is followed by