Human cytomegalovirus-specific CD4(+) T-cell clones recognize cross-reactive peptides from the immediate early 1 protein.

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.