Degradation of the immunogenic peptide gp100(280-288) by the monocyte-like U937 cell line.
The possible degradation of the tumor antigen epitope gp100(280-288) (YLEPGPVTA) in the presence of the monocyte-like line U937, and the effect of degradation on the in vitro-measured immune recognition, were investigated by chromatographic techniques and immunological assays. Results indicate a rapid hydrolysis of the substrate in the presence of the model cells, which is consistent with the hypothesis that degradation of gp100(280-288) is caused by the activity of U937-expressed enzymes, specifically amino- and carboxypeptidases. On the other hand, these results do not support the involvement of other enzymes known to be expressed by U937 cells. From a functional point of view, these data indicate that the degradation of gp100(280-288) severely hampered recognition by specific CTL clones. The results obtained may provide a model for epitope degradation by the antigen-presenting cells found in defined anatomical compartments and may, at least in part, account for the low activity of peptide-based antineoplastic vaccines, as well as for the transience of the effects of subcutaneously administered peptides in general.
Albo
Federica
F
Dipartimento di Neuroscienze, Università Degli Studi di Roma "Tor Vergata", Via Montpellier 1, 00133 Rome, Italy.
Cavazza
Antonella
A
Giardina
Bruno
B
Lippa
Silvio
S
Marini
Mario
M
Roda
L Giorgio
LG
Spagnoli
Giulio
G
D000596:Amino Acids / Q000378:metabolism; D000951:Antigens, Neoplasm / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D006868:Hydrolysis; D007700:Kinetics; D008545:Melanoma / Q000737:chemistry / Q000276:immunology; D009000:Monocytes / Q000378:metabolism*; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D020298:U937 Cells
D000596:Amino Acids; D000951:Antigens, Neoplasm; D010446:Peptide Fragments