Yellow fever virus 17D envelope and NS3 proteins are major targets of the antiviral T cell response in mice.
The yellow fever virus 17D vaccine strain is one of the most effective and safe vaccines available. The immune response after immunization is characterized by long-lasting high titers of neutralizing antibodies. Here, we have initiated a characterization of YFV-17D-specific cellular immune responses. This study makes three points. First, we have identified two CD8 T cell epitopes and one CD4 T cell epitope. An H-2Kb-restricted dominant epitope was mapped in the NS3 protein, whereas the viral envelope protein harbored an H-2Db-restricted subdominant epitope and the I-Ab-restricted CD4 T cell epitope. Second, illustrating the concept of immunodomination, we found that after abrogation of the dominant response in H-2Kb knockout mice, the frequencies of T cells recognizing the subdominant Db-restricted epitope increased dramatically. Finally, the H-2Db-restricted epitope lacks the canonical Asn anchor residue at position 5, indicating that epitopes may be missed by strict application of the H-2Db-binding motif. Identification of these T cell epitopes will facilitate studies on the cellular immunity against YFV-based expression or immunization vectors.
van der Most
Robbert G
RG
Emory Vaccine Center, Emory University School of Medicine, Atlanta, Georgia 30322, USA. r.g.vandermost@vet.uu.nl
Harrington
Laurie E
LE
Giuggio
Vicki
V
Mahar
Patryce L
PL
Ahmed
Rafi
R
D000818:Animals; D015704:CD4 Antigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002452:Cell Count; D002478:Cells, Cultured; D000939:Epitopes / Q000032:analysis; D005260:Female; D005434:Flow Cytometry; D006183:H-2 Antigens / Q000235:genetics / Q000276:immunology; D007111:Immunity, Cellular; D007371:Interferon-gamma / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013997:Time Factors; D014759:Viral Envelope Proteins / Q000276:immunology*; D017361:Viral Nonstructural Proteins / Q000276:immunology*; D015004:Yellow Fever / Q000276:immunology* / Q000517:prevention & control; D022341:Yellow Fever Vaccine / Q000008:administration & dosage; D015005:Yellow fever virus / Q000276:immunology* / Q000378:metabolism
D015704:CD4 Antigens; D000939:Epitopes; D006183:H-2 Antigens; D014759:Viral Envelope Proteins; D017361:Viral Nonstructural Proteins; D022341:Yellow Fever Vaccine; C078400:yellow fever virus envelope protein E; D007371:Interferon-gamma