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-1 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-1 in 40% of subjects. CD4+ T cell responses to pp65 were detected in 50% of subjects, but none were detected to IE-1. Several new IE-1 HLA class I epitopes were identified, including 4 restricted to HLA-C antigens. One region of IE-1 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.


CONCLUSIONS
Since naturally occurring CD4+ and CD8+ T cell responses to pp65 were detectable in many subjects, but only CD8+ T cell responses to IE-1 were detected, pp65 may be better than IE-1 for use in vaccine and adoptive immune therapies.
Slezak
Stefanie L
SL
Department of Transfusion Medicine, Warren G Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland, USA. sslezak@cc.nih.gov
Bettinotti
Maria
M
Selleri
Silvia
S
Adams
Sharon
S
Marincola
Francesco M
FM
Stroncek
David F
DF
D000293:Adolescent; D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D003587:Cytomegalovirus / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D006680:HLA Antigens / Q000235:genetics; D006262:Health; D006801:Humans; D017874:Immediate-Early Proteins / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D019151:Peptide Library; D010455:Peptides / Q000276:immunology; D010750:Phosphoproteins / Q000276:immunology*; D014763:Viral Matrix Proteins / Q000276:immunology*; D055815:Young Adult
D018984:Epitopes, T-Lymphocyte; D006680:HLA Antigens; C088645:IE1 protein, cytomegalovirus; D017874:Immediate-Early Proteins; D019151:Peptide Library; D010455:Peptides; D010750:Phosphoproteins; D014763:Viral Matrix Proteins; C065418:cytomegalovirus matrix protein 65kDa; D007371:Interferon-gamma