Human Cytomegalovirus-Specific CD4 + T-Cell Clones Recognize Cross-Reactive Peptides From the Immediate Early 1 Protein

Abstract

Human cytomegalovirus (HCMV) is a β-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 HLADR8 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.