CD8+ cell activation to a major mastocytoma rejection antigen, P815AB: requirement for tum- or helper peptides in priming for skin test reactivity to a P815AB-related peptide.
Delayed-type hypersensitivity (DTH) responses, mediated by CD8+ cells and detected by skin test assay, occur in sensitized mice in response to challenge with class I-restricted antigenic peptides of mutagenized (tum-) P815 mastocytoma cells. In contrast, a nonapeptide related to a tumor rejection antigen, P815AB, failed in this study to elicit DTH after sensitization of mice with irradiated tumor cells or adoptive transfer of P815AB-pulsed dendritic cells. Unresponsiveness, however, could be overcome by immunization with tumor cells co-expressing P815AB and tum- antigens. When used for cell pulsing in vitro, a mixture of P815AB and tum- peptides was also highly effective in inducing anti-P815AB reactivity, as was the combined use of P815AB and class II-restricted peptides of tetanus toxin or Plasmodium berghei circumsporozoite protein. While the effector phase of the CD8+ cell-mediated DTH to P815AB was unaffected by the ablation of CD4+ cells, the same treatment, or neutralization of IFN-gamma, negated the induction of reactivity if it occurred at the time of sensitization. Thus, defective activation of CD4+ cells may contribute to the poor immunogenicity of P815AB. Besides providing an insight into the mechanisms of anti-tumor protection induced by tum- cells, these data offer useful information for the design of vaccination strategies against identified tumor antigens.
Grohmann
U
U
Department of Experimental Medicine, University of Perugia, Italy.
Bianchi
R
R
Fioretti
M C
MC
Fallarino
F
F
Binaglia
L
L
Uyttenhove
C
C
Van Pel
A
A
Boon
T
T
Puccetti
P
P
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology*; D000953:Antigens, Protozoan / Q000737:chemistry / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D006084:Graft Rejection / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006968:Hypersensitivity, Delayed / Q000276:immunology*; D007114:Immunization; D016219:Immunotherapy, Adoptive; D007939:Leukemia L1210 / Q000473:pathology; D008213:Lymphocyte Activation; D008212:Lymphocyte Depletion; D008297:Male; D012515:Mast-Cell Sarcoma / Q000276:immunology*; D051379:Mice; D008811:Mice, Inbred DBA; D008969:Molecular Sequence Data; D009368:Neoplasm Transplantation / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology*; D010962:Plasmodium berghei / Q000276:immunology; D015800:Protozoan Proteins / Q000737:chemistry / Q000276:immunology; D051381:Rats; D012882:Skin Tests; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013744:Tetanus Toxin / Q000737:chemistry / Q000276:immunology; D014162:Transfection
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D000953:Antigens, Protozoan; D000949:Histocompatibility Antigens Class II; D010446:Peptide Fragments; D015800:Protozoan Proteins; D013744:Tetanus Toxin; C041595:circumsporozoite protein, Protozoan; C076546:tumor rejection antigen P815A, mouse