CMV pp65 and IE-1 T cell epitopes recognized by healthy subjects

Background: Adoptive immune and vaccine therapies have been used to prevent cytomegalovirus ( CMV) disease in recipients of hematopoietic progenitor cell transplants, but the nature of T cell responses to CMV have not been completely characterized. Methods: Peptide pools and individual peptides derived from the immune-dominant CMV proteins pp65 and IE-I and antigen-specific, cytokine flow cytometry were used to characterize the prevalence and frequency of CD4+ and CD8+ memory T cells in 20 healthy CMV-seropositive subjects. Results: CD8+ T cell responses to pp65 were detected in 35% of subjects and to IE-I in 40% of subjects. CD4+ T cell responses to pp65 were detected in 50% of subjects, but none were detected to IE-I. Several new IE-I HLA class I epitopes were identified, including 4 restricted to HLA-C antigens. One region of IE-I spanning amino acids 300 to 327 was rich in class I epitopes. The HLA class I restrictions of IE-1 peptides were more promiscuous than those of pp65 peptides. Conclusion: Since naturally occurring CD4+ and CD8+ T cell responses to pp65 were detectable in many subjects, but only CD8+ T cell responses to IE-I were detected, pp65 may be better than IE-I for use in vaccine and adoptive immune therapies.