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In the absence of aminopeptidase ERAAP, MHC class I molecules present many unstable and highly immunogenic peptides

In the absence of aminopeptidase ERAAP, MHC class I molecules present many unstable and highly immunogenic peptides
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.
1529-2908
101-108
Hammer, Gianna Elena
a5b87a5a-f410-418b-86db-e119d30429b8
Gonzalez, Federico
b318014e-3984-4696-87c6-a89a3ac326e0
James, Edward
7dc1afb7-d326-4050-89fc-1f4e2a1a19a4
Nolla, Hector
a1eeee77-c235-4139-8ea8-d3a6ce6d8cdd
Shastri, Nilabh
8af29105-c59b-4260-bdde-a97c016e0793
Hammer, Gianna Elena
a5b87a5a-f410-418b-86db-e119d30429b8
Gonzalez, Federico
b318014e-3984-4696-87c6-a89a3ac326e0
James, Edward
7dc1afb7-d326-4050-89fc-1f4e2a1a19a4
Nolla, Hector
a1eeee77-c235-4139-8ea8-d3a6ce6d8cdd
Shastri, Nilabh
8af29105-c59b-4260-bdde-a97c016e0793

Hammer, Gianna Elena, Gonzalez, Federico, James, Edward, Nolla, Hector and Shastri, Nilabh (2007) In the absence of aminopeptidase ERAAP, MHC class I molecules present many unstable and highly immunogenic peptides. Nature Immunology, 8 (1), 101-108. (doi:10.1038/ni1409).

Record type: Article

Abstract

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.

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Published date: 2007

Identifiers

Local EPrints ID: 44604
URI: http://eprints.soton.ac.uk/id/eprint/44604
ISSN: 1529-2908
PURE UUID: 7789d048-642b-4c32-9721-9fc3c3926a2b
ORCID for Edward James: ORCID iD orcid.org/0000-0001-8638-7928

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Date deposited: 06 Mar 2007
Last modified: 16 Mar 2024 03:51

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Contributors

Author: Gianna Elena Hammer
Author: Federico Gonzalez
Author: Edward James ORCID iD
Author: Hector Nolla
Author: Nilabh Shastri

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