Monoclonal antibody detection of a major self peptide. MHC class II complex.
MHC class I and class II molecules transport foreign and self peptides to the cell surface and present them to T lymphocytes. Detection of these peptide:MHC complexes has thus far been limited to analysis of the response of a T cell. Previously, we showed that a mAb, Y-Ae, reacts with 10 to 15% of class II molecules on peripheral B lymphocytes and on cells in the thymus medulla but not thymus cortex in mice that express both I-Ab and I-Eb molecules. Elsewhere, we show that Y-Ae detects a self E alpha peptide bound to I-Ab molecules. Data presented here suggest that the antibody binds over the peptide binding groove of class II molecules, and, like a TCR, appears to recognize both the self peptide and polymorphic class II residues. In addition to B lymphocytes, the Y-Ae determinant is expressed at comparable levels on other APC, including macrophages and dendritic cells. Finally, the antibody does not react with invariant chain-associated class II complexes, thus providing direct evidence that invariant chain:class II complexes and peptide:class II complexes are mutually exclusive. These data provide further evidence that immunologic self is of limited complexity, and have important implications for T cell selection, self tolerance, and autoreactivity.
Murphy
D B
DB
Laboratory of Immunology, Wadsworth Center, New York State Department of Health, Albany 12201.
Rath
S
S
Pizzo
E
E
Rudensky
A Y
AY
George
A
A
Larson
J K
JK
Janeway
C A
CA
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000938:Antigen-Presenting Cells / Q000276:immunology; D000944:Antigens, Differentiation, B-Lymphocyte; D001324:Autoantigens / Q000737:chemistry / Q000276:immunology*; D001665:Binding Sites; D000939:Epitopes; D000949:Histocompatibility Antigens Class II / Q000276:immunology* / Q000378:metabolism; D046911:Macromolecular Substances; D008285:Major Histocompatibility Complex; D051379:Mice; D008815:Mice, Inbred Strains; D015394:Molecular Structure; D010455:Peptides / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology; D014018:Tissue Distribution
D000911:Antibodies, Monoclonal; D000944:Antigens, Differentiation, B-Lymphocyte; D001324:Autoantigens; D000939:Epitopes; D000949:Histocompatibility Antigens Class II; C024138:I-E-antigen; D046911:Macromolecular Substances; D010455:Peptides; C045084:invariant chain