In the absence of aminopeptidase ERAAP, MHC class I molecules present many unstable and highly immunogenic peptides.
Immunosurveillance by cytotoxic T cells requires that cells generate a diverse spectrum of peptides for presentation by major histocompatibility complex (MHC) class I molecules. Those peptides are generated by proteolysis, which begins in the cytoplasm and continues in the endoplasmic reticulum by the unique aminopeptidase ERAAP. The overall extent to which trimming by ERAAP modifies the peptide pool and the immunological consequences of ERAAP deficiency are unknown. Here we show that the peptide-MHC repertoire of ERAAP-deficient mice was missing many peptides. Furthermore, ERAAP-deficient cells presented many unstable and structurally unique peptide-MHC complexes, which elicited potent CD8+ T cell and B cell responses. Thus, ERAAP is a 'quintessential editor' of the peptide-MHC repertoire and, paradoxically, its absence enhances immunogenicity.
Hammer
Gianna Elena
GE
Division of Immunology, Department of Molecular and Cell Biology, University of California, Berkeley, California 94720, USA.
Gonzalez
Federico
F
James
Edward
E
Nolla
Hector
H
Shastri
Nilabh
N
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D007931:Leucyl Aminopeptidase / Q000172:deficiency* / Q000235:genetics; D008024:Ligands; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010455:Peptides / Q000276:immunology*
D015395:Histocompatibility Antigens Class I; D008024:Ligands; D010455:Peptides; D007931:Leucyl Aminopeptidase; C456799:puromycin-insensitive leucyl-specific aminopeptidase