Epitope mapping of full-length glycoprotein D from HSV-2 reveals a novel CD4+ CTL epitope located at the transmembrane-cytoplasmic junction.
The glycoprotein D of HSV-2 (gD2) is currently a leading candidate vaccine target for genital herpes vaccines as both cellular and humoral responses can be generated against it. However, little is known about how vaccine composition will affect T cell epitope selection. A panel of 15-mer peptides (with 11 amino acid overlap) spanning full-length gD2 was used to investigate the fine specificity of T cell responses to gD2 as well as the role of vaccine composition on epitope selection. Spleen cells from BALB/c mice (H-2(d)) immunized with gD2, formulated with or without AlPO(4) and/or IL-12, were stimulated in vitro with overlapping gD2 peptides. Cellular responses (lymphoproliferation and IFN-gamma expression) were mapped to four epitopes within the gD2 molecule: gD2(49-63), gD2(105-119), gD2(245-259), and gD2(333-347). CTL analysis of these four epitopes indicated that not all of them could serve as a CTL epitope. Mice immunized with gD2 expressed from a viral vector mounted CTL responses primarily to one epitope located in the extracellular domain of gD2 (gD2(245-259)). More importantly, mice immunized with gD2 co-administered with IL-12 mounted CTL responses to an additional epitope located at the transmembrane-cytoplasmic junction of gD2 (gD2(333-347)). The location of this novel epitope emphasizes the benefit of using full-length versions of glycoproteins when designing vaccine components.
Cooper
David
D
Department of Vaccines Discovery Research, Wyeth Research, Pearl River, NY 10965, USA. cooperd3@wyeth.com
Mester
Joseph C
JC
Guo
Min
M
Nasar
Farooq
F
Souza
Victor
V
Dispoto
Sharon
S
Sidhu
Maninder
M
Hagen
Michael
M
Eldridge
John H
JH
Natuk
Robert J
RJ
Pride
Michael W
MW
D000595:Amino Acid Sequence; D000818:Animals; D015704:CD4 Antigens / Q000378:metabolism*; D016466:CHO Cells; D002462:Cell Membrane / Q000276:immunology*; D002522:Chlorocebus aethiops; D006224:Cricetinae; D003412:Cricetulus; D003593:Cytoplasm / Q000276:immunology*; D018604:Epitope Mapping; D018984:Epitopes, T-Lymphocyte / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D018258:Herpesvirus 2, Human / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology*
D015704:CD4 Antigens; D018984:Epitopes, T-Lymphocyte; D010446:Peptide Fragments; D014759:Viral Envelope Proteins; C040570:glycoprotein D-herpes simplex virus type 2