title: Human cytomegalovirus-specific CD4(+) T-cell clones recognize cross-reactive peptides from the immediate early 1 protein.
abstract: Human cytomegalovirus (HCMV) is a beta-herpes virus that persists in a latent state in immunocompetent individuals. Both CD4(+) and CD8(+) T lymphocytes have been reported to be present at a high frequency in HCMV-seropositive individuals and are involved in the control of infection. How such frequencies are maintained is not completely understood. We have observed that the canonical HLA-DR8 epitope of the immediate early 1 protein (IE1) contained in the IE1 (156--175) sequence shares homologies with an IE1 sequence contained in part in the previously reported HLA-DR3 epitope, IE1 (91-110). We thus wondered whether such homology in a single protein would translate into recognition of the IE1 homolog sequence by HLA-DR8-restricted CD4(+) cells in addition to the canonical epitope. We found that established HLA-DR8-restricted T cell clones are also able to cross-recognize the IE1 (91--110) peptide, as well as a shorter 14-mer, IE1 (91--104). Moreover, the homolog peptide IE1 (91-110) was able to generate, from a seropositive blood donor, new IE1-specific, HLA-DR8-restricted CD4(+) T cell clones that were also cross-reactive. Those findings may provide clues to the formation and regulation of the T-cell repertoire and memory.
authors.affiliation: INSERM U563, Toulouse, CPTP, Institut Claude de Préval, Toulouse Cedex, France.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Le Roy
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Davignon
mesh_terms: D000595:Amino Acid Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002999:Clone Cells / Q000276:immunology; D003429:Cross Reactions; D003587:Cytomegalovirus / Q000276:immunology* / Q000378:metabolism; D006684:HLA-DR Antigens / Q000378:metabolism; D059810:HLA-DR Serological Subtypes; D006801:Humans; D017874:Immediate-Early Proteins / Q000737:chemistry / Q000276:immunology*; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000276:immunology*; D015375:Receptors, Interleukin-2; D014764:Viral Proteins / Q000737:chemistry / Q000276:immunology*
chemical_list: D006684:HLA-DR Antigens; D059810:HLA-DR Serological Subtypes; C041559:HLA-DR8 antigen; C088645:IE1 protein, cytomegalovirus; D017874:Immediate-Early Proteins; D010455:Peptides; D015375:Receptors, Interleukin-2; D014764:Viral Proteins