Competition for Access to the Rat Major Histocompatibility Complex Class I Peptide-loading Complex Reveals Optimization of Peptide Cargo in the Absence of Transporter Associated with Antigen Processing (TAP) Association

Stuart Ford, Antony Antoniou, Geoffrey W. Butcher, Simon J. Powis*

*Corresponding author for this work

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9 Citations (Scopus)
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Abstract

Major histocompatibility complex (MHC) class I molecules load peptides in the endoplasmic reticulum in a process during which the peptide cargo is normally optimized in favor of stable MHC-peptide interactions. A dynamic multimolecular assembly termed the peptide-loading complex (PLC) participates in this process and is composed of MHC class I molecules, calreticulin, ERp57, and tapasin bound to the transporter associated with antigen processing (TAP) peptide transporter. We have exploited the observation that the rat MHC class I allele RT1-Aa, when expressed in the rat C58 thymoma cell line, effectively competes and prevents the endogenous RT1-Au molecule from associating with TAP. However, stable RT1-Au molecules are assembled efficiently in competition with RT1-Aa, demonstrating that cargo optimization can occur in the absence of TAP association. Defined mutants of RT1-Aa, which do not allow formation of the PLC, fail to become thermostable in C58 cells. Wild-type RT1-Aa, which does allow PLC formation, also fails to become thermostable in this cell line, which carries the rat TAPB transporter that supplies peptides incompatible for RT1-A a binding. Full optimization of RT1-Aa requires the presence of the TAP2A allele, which is capable of supplying suitable peptides. Thus, formation of the PLC alone is not sufficient for optimization of the MHC class I peptide cargo.

Original languageEnglish
Pages (from-to)16077-16082
Number of pages6
JournalJournal of Biological Chemistry
Volume279
Issue number16
DOIs
Publication statusPublished - 16 Apr 2004
Externally publishedYes

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