Expression of a membrane protease enhances presentation of endogenous antigens to MHC class I-restricted T lymphocytes.
We find that expression of the membrane dipeptidyl carboxypeptidase angiotensin-converting enzyme (ACE) enhances presentation of certain endogenously synthesized peptides to major histocompatibility complex (MHC) class I-restricted cytotoxic T lymphocytes. ACE appears to function only in an intracellular secretory compartment of antigen-presenting cells. ACE-enhanced antigen presentation requires the expression of the putative antigenic peptide transporters, TAP1 and TAP2. These findings demonstrate that a protease can influence the processing of endogenously synthesized antigens and strongly suggest that longer peptides can be transported from the cytosol to a secretory compartment where trimming of antigenic peptides to the lengths preferred by MHC class I molecules can occur if the appropriate protease is present.
Eisenlohr
L C
LC
Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20906.
Bacik
I
I
Bennink
J R
JR
Bernstein
K
K
Yewdell
J W
JW
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters; D000595:Amino Acid Sequence; D000818:Animals; D000938:Antigen-Presenting Cells / Q000201:enzymology*; D002352:Carrier Proteins / Q000378:metabolism*; D002460:Cell Line; D010450:Endopeptidases / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000096:biosynthesis*; D008969:Molecular Sequence Data; D009154:Mutation; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters; D002352:Carrier Proteins; D000949:Histocompatibility Antigens Class II; D008565:Membrane Proteins; C073119:TAP1 protein, human; C071692:TAP2 protein, human; D010450:Endopeptidases; D007703:Peptidyl-Dipeptidase A