Roles for asparagine endopeptidase in class II MHC-restricted antigen processing.
The adaptive immune response depends on the creation of suitable peptides from foreign antigens for display on MHC molecules to T lymphocytes. Similarly, MHC-restricted display of peptides derived from self proteins results in the elimination of many potentially autoreactive T cells. Different proteolytic systems are used to generate the peptides that are displayed as T cell epitopes on class I compared with class II MHC molecules. In the case of class II MHC molecules, the proteases that reside within the endosome/lysosome system of antigen-presenting cells are responsible; surprisingly, however, there are relatively few data on which enzymes are involved. Recently we have asked whether proteolysis is required simply in a generic sense, or whether the action of particular enzymes is needed to generate specific class II MHC-associated T cell epitopes. Using the recently identified mammalian asparagine endopeptidase as an example, we review recent evidence that individual enzymes can make clear and non-redundant contributions to MHC-restricted peptide display.
Division of Cell Biology & Immunology, School of Life Sciences, University of Dundee, Dundee DDI 5EH, U.K. c.watts@dundee.ac.uk
Colin
C
Watts
Daniela
D
Mazzeo
Michelle A
MA
West
Stephen P
SP
Matthews
Doreen
D
Keane
Garth
G
Hamilton
Linda V
LV
Persson
Jennifer M
JM
Lawson
Bénédicte
B
Manoury
Catherine X
CX
Moss
D000595:Amino Acid Sequence; D000818:Animals; D002451:Cell Compartmentation; D010450:Endopeptidases / Q000378:metabolism*; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D008969:Molecular Sequence Data
D000949:Histocompatibility Antigens Class II; D010450:Endopeptidases