Cutting edge: introduction of an endopeptidase cleavage motif into a determinant flanking region of hen egg lysozyme results in enhanced T cell determinant display.
The choice of which determinants of a whole Ag will be presented on cell surface MHC class II molecules after uptake and processing by APC is the result of the interplay between structural characteristics of the Ag and the processing machinery of the APC. In this study, we demonstrate that introduction of a dibasic motif adjacent to a subdominant determinant enhances the presentation of this determinant from the whole molecule. This is the first report showing that a single amino acid substitution in a whole Ag, designed to introduce an endopeptidase recognition site, enhances display of class II-restricted determinants, most likely by creating a peptide chain cleavage in the antigenic molecule. Our findings have important implications for the understanding of immunodominance and for vaccine design.
Schneider
S C
SC
Division of Immune Regulation, La Jolla Institute for Allergy and Immunology, San Diego, CA 92121, USA. sus@liai.org
Ohmen
J
J
Fosdick
L
L
Gladstone
B
B
Guo
J
J
Ametani
A
A
Sercarz
E E
EE
Deng
H
H
D020816:Amino Acid Motifs / Q000276:immunology; D000818:Animals; D017951:Antigen Presentation; D002645:Chickens; D010450:Endopeptidases / Q000276:immunology* / Q000378:metabolism*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology / Q000378:metabolism*; D006183:H-2 Antigens / Q000276:immunology / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006825:Hybridomas; D006868:Hydrolysis; D016056:Immunodominant Epitopes / Q000276:immunology / Q000378:metabolism; D051379:Mice; D009113:Muramidase / Q000276:immunology / Q000378:metabolism*; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism
D018984:Epitopes, T-Lymphocyte; D006183:H-2 Antigens; D000949:Histocompatibility Antigens Class II; D016056:Immunodominant Epitopes; D010446:Peptide Fragments; D009113:Muramidase; D010450:Endopeptidases