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.
Dipartimento di Neuroscienze, Università Degli Studi di Roma "Tor Vergata", Via Montpellier 1, 00133 Rome, Italy.
Federica
F
Albo
Antonella
A
Cavazza
Bruno
B
Giardina
Silvio
S
Lippa
Mario
M
Marini
L Giorgio
LG
Roda
Giulio
G
Spagnoli
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