Induction of herpes simplex virus gB-specific cytotoxic T lymphocytes in TAP1-deficient mice by genetic immunization but not HSV infection.
Loading of most endogenous peptides on major histocompatibility complex class I molecules is conditional on their transport into the endoplasmic reticulum (ER) by the peptide transporter TAP. We describe an HSV-2/1 cross-reactive cytotoxic T-cell (CTL) epitope that is processed in a TAP1-independent manner in vivo following immunization of TAP1-/- mice with naked DNA or a recombinant vaccinia virus. These data indicated that TAP1-independent processing of endogenous proteins is sufficient to prime CTLs in vivo. TAP1-independent processing of this epitope was not due to ER targeting by signal sequences and exogenous loading of MHC-I molecules and was not influenced by the amino acids flanking this epitope. In contrast, TAP1-/- mice infected with HSV-2 or HSV-2 mutants did not mount a CTL response against this epitope.
Chiron Corporation, Emeryville, California 94608, USA. xavier_paliard@chiron.con
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X
Paliard
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B
Doe
M J
MJ
Selby
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K
Hartog
A Y
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Lee
R L
RL
Burke
C M
CM
Walker
D000818:Animals; D017951:Antigen Presentation; D002460:Cell Line; D003429:Cross Reactions; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D016326:Extracellular Matrix Proteins / Q000172:deficiency* / Q000235:genetics; D005260:Female; D006561:Herpes Simplex / Q000276:immunology / Q000517:prevention & control; D007114:Immunization; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000172:deficiency* / Q000235:genetics; D018139:Simplexvirus / Q000235:genetics / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D019444:Vaccines, DNA / Q000008:administration & dosage; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology; D014765:Viral Vaccines / Q000008:administration & dosage
D018984:Epitopes, T-Lymphocyte; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; D019444:Vaccines, DNA; D014759:Viral Envelope Proteins; D014765:Viral Vaccines; C044525:glycoprotein B, herpes simplex virus type 2