Comparative analysis of CD8+ T cell responses against human cytomegalovirus proteins pp65 and immediate early 1 shows similarities in precursor frequency, oligoclonality, and phenotype.
CD8+ T cells are key effectors of the immune response against human cytomegalovirus (HCMV). A number of HCMV-derived CD8+ T cell epitopes are known. Using epitope prediction and subsequent testing for interferon-gamma responses by the ELISPOT assay, we identified an optimal human leukocyte antigen (HLA)-A*0201-restricted CD8+ 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 (CD57+ and CD28-), with considerable restriction in T cell receptor beta-chain variable region use. The results confirm that, although pp65 is a major target for CD8+ T cells, the IE-1 protein may itself stimulate comparable responses in some persons.
Khan
Naeem
N
Cancer Research UK Institute for Cancer Studies, University of Birmingham, Vincent Drive, Edgbaston, Birmingham, UK B15 2TA.
Cobbold
Mark
M
Keenan
Russell
R
Moss
Paul A H
PA
D000956:Antigens, Viral / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D019674:Genes, T-Cell Receptor beta; D015234:HLA-A Antigens / Q000032:analysis; D015789:HLA-A2 Antigen; D006801:Humans; D017874:Immediate-Early Proteins / Q000276:immunology*; D016056:Immunodominant Epitopes; D007371:Interferon-gamma / Q000096:biosynthesis; D010641:Phenotype; D010750:Phosphoproteins / Q000276:immunology*; D014763:Viral Matrix Proteins / Q000276:immunology*
D000956:Antigens, Viral; D015234:HLA-A Antigens; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D017874:Immediate-Early Proteins; D016056:Immunodominant Epitopes; D010750:Phosphoproteins; D014763:Viral Matrix Proteins; C065418:cytomegalovirus matrix protein 65kDa; C044582:immediate-early proteins, cytomegalovirus; D007371:Interferon-gamma