Identification of proteases that process distinct epitopes on the same protein.
Proteolytic degradation of protein antigens is thought to be a major step in the processing of Ag for presentation to T cells, but the range of proteases involved is unknown. Here we used a large panel of protease inhibitors to determine the role of each of the four classes of proteases in antigen processing. Moreover, we asked whether different proteases were necessary for presentation of different known epitopes, defined by three Th cell clones. For all three epitopes of myoglobin, intracellular thiol proteases such as cathepsins B or L were the only proteases necessary. Furthermore, myoglobin pre-digested with cathepsin B could be presented to all three clones without further processing. Thus, a single protease may be both necessary and sufficient for Ag processing to present the majority of epitopes, at least for myoglobin. This finding provides an explanation of earlier data on the fragments produced from processed myoglobin, and so may contribute to a much needed solution to the long standing problem of predicting where a protein will be cleaved during processing.
Takahashi
H
H
Molecular Immunogenetics and Vaccine Research Section, National Cancer Institute, Bethesda, MD 20892.
Cease
K B
KB
Berzofsky
J A
JA
D000818:Animals; D000938:Antigen-Presenting Cells / Q000187:drug effects / Q000378:metabolism*; D000954:Antigens, Surface / Q000032:analysis; D002401:Cathepsin B / Q000494:pharmacology; D000939:Epitopes / Q000378:metabolism*; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D006868:Hydrolysis; D007976:Leupeptins / Q000494:pharmacology; D008297:Male; D051379:Mice; D009211:Myoglobin / Q000276:immunology / Q000378:metabolism; D010447:Peptide Hydrolases / Q000145:classification / Q000494:pharmacology*; D011480:Protease Inhibitors / Q000145:classification
D000954:Antigens, Surface; D000939:Epitopes; D000949:Histocompatibility Antigens Class II; D007976:Leupeptins; D009211:Myoglobin; D011480:Protease Inhibitors; D010447:Peptide Hydrolases; D002401:Cathepsin B; C032854:leupeptin