The exception that reinforces the rule: crosspriming by cytosolic peptides that escape degradation.
The nature of crosspriming immunogens for CD8(+) T cell responses is highly controversial. By using a panel of T cell receptor-like antibodies specific for viral peptides bound to mouse D(b) major histocompatibility complex class I molecules, we show that an exceptional peptide (PA(224-233)) expressed as a viral minigene product formed a sizeable cytosolic pool continuously presented for hours after protein synthesis was inhibited. PA(224-233) pool formation required active cytosolic heat-shock protein 90 but not ER g96 and uniquely enabled crosspriming by this peptide. These findings demonstrate that exceptional class I binding oligopeptides that escape proteolytic degradation are potent crosspriming agents. Thus, the feeble immunogenicity of natural proteasome products in crosspriming can be attributed to their evanescence in donor cells and not an absolute inability of cytosolic oligopeptides to be transferred to and presented by professional antigen-presenting cells.
Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Avital
A
Lev
Kazuyo
K
Takeda
Damien
D
Zanker
Jason C
JC
Maynard
Peniel
P
Dimberu
Elizabeth
E
Waffarn
James
J
Gibbs
Nir
N
Netzer
Michael F
MF
Princiotta
Len
L
Neckers
Didier
D
Picard
Christopher V
CV
Nicchitta
Weisan
W
Chen
Yoram
Y
Reiter
Jack R
JR
Bennink
Jonathan W
JW
Yewdell
D000818:Animals; D000906:Antibodies / Q000276:immunology; D000956:Antigens, Viral / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D002460:Cell Line; D005260:Female; D018841:HSP90 Heat-Shock Proteins / Q000276:immunology / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D009980:Influenza A virus / Q000276:immunology*; D051379:Mice; D010455:Peptides / Q000276:immunology* / Q000378:metabolism; D011994:Recombinant Proteins / Q000276:immunology / Q000378:metabolism
D000906:Antibodies; D000956:Antigens, Viral; D018841:HSP90 Heat-Shock Proteins; D015395:Histocompatibility Antigens Class I; D010455:Peptides; D011994:Recombinant Proteins