Abstract
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.
MeSH terms
-
ATP Binding Cassette Transporter, Subfamily B, Member 2
-
ATP Binding Cassette Transporter, Subfamily B, Member 3
-
ATP-Binding Cassette Transporters*
-
Amino Acid Sequence
-
Animals
-
Antigen-Presenting Cells / enzymology*
-
Carrier Proteins / metabolism*
-
Cell Line
-
Endopeptidases / metabolism*
-
Endoplasmic Reticulum / metabolism
-
Histocompatibility Antigens Class II / metabolism*
-
Humans
-
Membrane Proteins / biosynthesis*
-
Molecular Sequence Data
-
Mutation
-
Peptidyl-Dipeptidase A / metabolism*
-
T-Lymphocytes / metabolism
Substances
-
ATP Binding Cassette Transporter, Subfamily B, Member 2
-
ATP Binding Cassette Transporter, Subfamily B, Member 3
-
ATP-Binding Cassette Transporters
-
Carrier Proteins
-
Histocompatibility Antigens Class II
-
Membrane Proteins
-
TAP1 protein, human
-
TAP2 protein, human
-
Endopeptidases
-
Peptidyl-Dipeptidase A