Recombinant virus vaccination against "self" antigens using anchor-fixed immunogens.
To study the induction of anti-"self" CD8+ T-cell reactivity against the tumor antigen gp100, we used a mouse transgenic for a chimeric HLA-A*0201/H-2 Kb molecule (A2/Kb). We immunized the mice with a recombinant vaccinia virus encoding a form of gp100 that had been modified at position 210 (from a threonine to a methionine) to increase epitope binding to the restricting class I molecule. Immunogens containing the "anchor-fixed" modification elicited anti-self CD8+ T cells specific for the wild-type gp100(209-217) peptide pulsed onto target cells. More important, these cells specifically recognized the naturally presented epitope on the surface of an A2/Kb-expressing murine melanoma, B16. These data indicate that anchor-fixing epitopes could enhance the function of recombinant virus-based immunogens.
Irvine
K R
KR
Surgery Branch, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA.
Parkhurst
M R
MR
Shulman
E P
EP
Tupesis
J P
JP
Custer
M
M
Touloukian
C E
CE
Robbins
P F
PF
Yafal
A G
AG
Greenhalgh
P
P
Sutmuller
R P
RP
Offringa
R
R
Rosenberg
S A
SA
Restifo
N P
NP
D000818:Animals; D017951:Antigen Presentation / Q000235:genetics / Q000276:immunology; D015551:Autoimmunity / Q000235:genetics / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D019496:Cancer Vaccines / Q000235:genetics / Q000276:immunology*; D000939:Epitopes / Q000276:immunology; D015234:HLA-A Antigens / Q000235:genetics / Q000276:immunology*; D007111:Immunity, Cellular; D008546:Melanoma, Experimental / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D009363:Neoplasm Proteins / Q000235:genetics / Q000276:immunology*; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology*; D014162:Transfection; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology; D058951:gp100 Melanoma Antigen
D019496:Cancer Vaccines; D000939:Epitopes; D015234:HLA-A Antigens; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; D010446:Peptide Fragments; C548642:Pmel protein, mouse; D058951:gp100 Melanoma Antigen