TAP association influences the conformation of nascent MHC class I molecules

Barbara A L Owen, Larry R Pease

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

The influence of TAP-MHC class I interactions on peptide binding to the class I heavy chain is assessed during TAP-dependent assembly using Kb- specific Abs that recognize conformational changes induced by assembly with β2-microglobulin (β2m) and by peptide binding. A significant portion (45%) of Kb molecules in TAP+, RMA-derived microsomes are associated with the TAP complex as measured by coimmunoisolation of Kb using anti-TAP1 Abs, while only 20% of the Kb heavy chain molecules are isolated as Kbβ2m complexes with the α-Kb-specific Abs, Y-3 or K-10-56. The amount of Kb isolated with Y-3 and K-10-56 increases in proportion to transport and binding of peptide to the Kb molecules within the RMA microsomes. In contrast, less than 5% of the Kb within TAP2-RMA-S microsomes associated with the remaining TAP1 subunit. However, greater than 60% of Kb heavy chain is isolated as K-10-56- and Y-3-reactive Kbβ2m complexes. We propose that a TAP-MHC class I interaction serves to stabilize the MHC class I:β2m complex in an immature conformation (Y-3 and K-10-56 nonreactive) prior to high affinity peptide binding, preventing the export of class I molecules complexed with low affinity peptide ligands from the ER.

Original languageEnglish (US)
Pages (from-to)4677-4684
Number of pages8
JournalJournal of Immunology
Volume162
Issue number8
StatePublished - Apr 15 1999

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Peptides
Microsomes
Ligands

ASJC Scopus subject areas

  • Immunology

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TAP association influences the conformation of nascent MHC class I molecules. / Owen, Barbara A L; Pease, Larry R.

In: Journal of Immunology, Vol. 162, No. 8, 15.04.1999, p. 4677-4684.

Research output: Contribution to journalArticle

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abstract = "The influence of TAP-MHC class I interactions on peptide binding to the class I heavy chain is assessed during TAP-dependent assembly using Kb- specific Abs that recognize conformational changes induced by assembly with β2-microglobulin (β2m) and by peptide binding. A significant portion (45{\%}) of Kb molecules in TAP+, RMA-derived microsomes are associated with the TAP complex as measured by coimmunoisolation of Kb using anti-TAP1 Abs, while only 20{\%} of the Kb heavy chain molecules are isolated as Kbβ2m complexes with the α-Kb-specific Abs, Y-3 or K-10-56. The amount of Kb isolated with Y-3 and K-10-56 increases in proportion to transport and binding of peptide to the Kb molecules within the RMA microsomes. In contrast, less than 5{\%} of the Kb within TAP2-RMA-S microsomes associated with the remaining TAP1 subunit. However, greater than 60{\%} of Kb heavy chain is isolated as K-10-56- and Y-3-reactive Kbβ2m complexes. We propose that a TAP-MHC class I interaction serves to stabilize the MHC class I:β2m complex in an immature conformation (Y-3 and K-10-56 nonreactive) prior to high affinity peptide binding, preventing the export of class I molecules complexed with low affinity peptide ligands from the ER.",
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