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The cell biology of major histocompatibility complex class I assembly: towards a molecular understanding

The cell biology of major histocompatibility complex class I assembly: towards a molecular understanding
The cell biology of major histocompatibility complex class I assembly: towards a molecular understanding
Major histocompatibility complex class I (MHC I) proteins protect the host from intracellular pathogens and cellular abnormalities through the binding of peptide fragments derived primarily from intracellular proteins. These peptide-MHC complexes are displayed at the cell surface for inspection by cytotoxic T lymphocytes. Here we reveal how MHC I molecules achieve this feat in the face of numerous levels of quality control. Among these is the chaperone tapasin, which governs peptide selection in the endoplasmic reticulum as part of the peptide-loading complex, and we propose key amino acid interactions central to the peptide selection mechanism. We discuss how the aminopeptidase ERAAP fine-tunes the peptide repertoire available to assembling MHC I molecules, before focusing on the journey of MHC I molecules through the secretory pathway, where calreticulin provides additional regulation of MHC I expression. Lastly we discuss how these processes culminate to influence immune responses.
major histocompatibility complex, antigen presentation, peptide selection, peptide loading complex, tapasin, eraap, calreticulin, immunodominance
0001-2815
259-75
Van Hateren, A.
e345fa3c-d89c-4b91-947e-c1d818cc7f71
James, E.
7dc1afb7-d326-4050-89fc-1f4e2a1a19a4
Bailey, A.
541e2cd9-ac72-4058-9293-def64fc2c284
Phillips, A.
a6255ffa-d42d-4eba-b15f-fd524eee7718
Dalchau, N.
8fb4b121-1642-4d4a-a7c8-854e5fda8540
Elliott, T.
16670fa8-c2f9-477a-91df-7c9e5b453e0e
Van Hateren, A.
e345fa3c-d89c-4b91-947e-c1d818cc7f71
James, E.
7dc1afb7-d326-4050-89fc-1f4e2a1a19a4
Bailey, A.
541e2cd9-ac72-4058-9293-def64fc2c284
Phillips, A.
a6255ffa-d42d-4eba-b15f-fd524eee7718
Dalchau, N.
8fb4b121-1642-4d4a-a7c8-854e5fda8540
Elliott, T.
16670fa8-c2f9-477a-91df-7c9e5b453e0e

Van Hateren, A., James, E., Bailey, A., Phillips, A., Dalchau, N. and Elliott, T. (2010) The cell biology of major histocompatibility complex class I assembly: towards a molecular understanding. Tissue Antigens, 76 (4), 259-75. (doi:10.1111/j.1399-0039.2010.01550.x). (PMID:21050182)

Record type: Article

Abstract

Major histocompatibility complex class I (MHC I) proteins protect the host from intracellular pathogens and cellular abnormalities through the binding of peptide fragments derived primarily from intracellular proteins. These peptide-MHC complexes are displayed at the cell surface for inspection by cytotoxic T lymphocytes. Here we reveal how MHC I molecules achieve this feat in the face of numerous levels of quality control. Among these is the chaperone tapasin, which governs peptide selection in the endoplasmic reticulum as part of the peptide-loading complex, and we propose key amino acid interactions central to the peptide selection mechanism. We discuss how the aminopeptidase ERAAP fine-tunes the peptide repertoire available to assembling MHC I molecules, before focusing on the journey of MHC I molecules through the secretory pathway, where calreticulin provides additional regulation of MHC I expression. Lastly we discuss how these processes culminate to influence immune responses.

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More information

Published date: October 2010
Keywords: major histocompatibility complex, antigen presentation, peptide selection, peptide loading complex, tapasin, eraap, calreticulin, immunodominance

Identifiers

Local EPrints ID: 168563
URI: http://eprints.soton.ac.uk/id/eprint/168563
ISSN: 0001-2815
PURE UUID: 2ecda6b4-cfda-4b51-9779-0a99b202366f
ORCID for A. Van Hateren: ORCID iD orcid.org/0000-0002-3915-0239
ORCID for E. James: ORCID iD orcid.org/0000-0001-8638-7928
ORCID for A. Bailey: ORCID iD orcid.org/0000-0003-0023-8679
ORCID for T. Elliott: ORCID iD orcid.org/0000-0003-1097-0222

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Date deposited: 30 Nov 2010 15:08
Last modified: 14 Mar 2024 02:59

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Contributors

Author: A. Van Hateren ORCID iD
Author: E. James ORCID iD
Author: A. Bailey ORCID iD
Author: A. Phillips
Author: N. Dalchau
Author: T. Elliott ORCID iD

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