Thermolabile H-2Kb molecules expressed by transporter associated with antigen processing-deficient RMA-S cells are occupied by low-affinity peptides

A. Dharshan De Silva, Alina Boesteanu, Rui Song, Nancy Nagy, Edward Harhaj, Clifford V. Harding, Sebastian Joyce

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

RMA-S cells do not express functional TAP, yet they express MHC class I molecules at the cell surface, especially at reduced temperatures (26°C). It is generally assumed that such class I molecules are 'empty,' devoid of any associated peptide. A radiochemical approach was used to label class I- associated peptides and to determine the extent to which Kb molecules in RMA-S cells are associated with peptides. These studies revealed that at 26°C Kb molecules in RMA-S cells are occupied with self-peptides. Such peptides stably associate with Kb at 26°C but easily dissociate from them at 37°C, suggesting low-affinity interactions between Kb and the associated peptides. At 26°C, at least some of these Kb molecules are stably expressed in a peptide-receptive state on the cell surface, whereas at 37°C they are short lived and are only transiently capable of binding and presenting exogenously supplied OVA 257-264 peptide for presentation to CD8+ Kb- restricted T lymphocytes. Thus contrary to current models of class I assembly in TAP-deficient RMA-S cells, the presumably 'empty' molecules are in fact associated with peptides at 26°C. Together, our data support the existence of an alternative mechanism of peptide binding and display by MHC class I molecules in TAP-deficient cells that could explain their ability to present Ag.

Original languageEnglish (US)
Pages (from-to)4413-4420
Number of pages8
JournalJournal of Immunology
Volume163
Issue number8
StatePublished - Jan 1 1999

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Antigen Presentation
Peptides
T-Lymphocytes
Temperature

All Science Journal Classification (ASJC) codes

  • Immunology

Cite this

De Silva, A. Dharshan ; Boesteanu, Alina ; Song, Rui ; Nagy, Nancy ; Harhaj, Edward ; Harding, Clifford V. ; Joyce, Sebastian. / Thermolabile H-2Kb molecules expressed by transporter associated with antigen processing-deficient RMA-S cells are occupied by low-affinity peptides. In: Journal of Immunology. 1999 ; Vol. 163, No. 8. pp. 4413-4420.
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abstract = "RMA-S cells do not express functional TAP, yet they express MHC class I molecules at the cell surface, especially at reduced temperatures (26°C). It is generally assumed that such class I molecules are 'empty,' devoid of any associated peptide. A radiochemical approach was used to label class I- associated peptides and to determine the extent to which Kb molecules in RMA-S cells are associated with peptides. These studies revealed that at 26°C Kb molecules in RMA-S cells are occupied with self-peptides. Such peptides stably associate with Kb at 26°C but easily dissociate from them at 37°C, suggesting low-affinity interactions between Kb and the associated peptides. At 26°C, at least some of these Kb molecules are stably expressed in a peptide-receptive state on the cell surface, whereas at 37°C they are short lived and are only transiently capable of binding and presenting exogenously supplied OVA 257-264 peptide for presentation to CD8+ Kb- restricted T lymphocytes. Thus contrary to current models of class I assembly in TAP-deficient RMA-S cells, the presumably 'empty' molecules are in fact associated with peptides at 26°C. Together, our data support the existence of an alternative mechanism of peptide binding and display by MHC class I molecules in TAP-deficient cells that could explain their ability to present Ag.",
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Thermolabile H-2Kb molecules expressed by transporter associated with antigen processing-deficient RMA-S cells are occupied by low-affinity peptides. / De Silva, A. Dharshan; Boesteanu, Alina; Song, Rui; Nagy, Nancy; Harhaj, Edward; Harding, Clifford V.; Joyce, Sebastian.

In: Journal of Immunology, Vol. 163, No. 8, 01.01.1999, p. 4413-4420.

Research output: Contribution to journalArticle

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AU - De Silva, A. Dharshan

AU - Boesteanu, Alina

AU - Song, Rui

AU - Nagy, Nancy

AU - Harhaj, Edward

AU - Harding, Clifford V.

AU - Joyce, Sebastian

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N2 - RMA-S cells do not express functional TAP, yet they express MHC class I molecules at the cell surface, especially at reduced temperatures (26°C). It is generally assumed that such class I molecules are 'empty,' devoid of any associated peptide. A radiochemical approach was used to label class I- associated peptides and to determine the extent to which Kb molecules in RMA-S cells are associated with peptides. These studies revealed that at 26°C Kb molecules in RMA-S cells are occupied with self-peptides. Such peptides stably associate with Kb at 26°C but easily dissociate from them at 37°C, suggesting low-affinity interactions between Kb and the associated peptides. At 26°C, at least some of these Kb molecules are stably expressed in a peptide-receptive state on the cell surface, whereas at 37°C they are short lived and are only transiently capable of binding and presenting exogenously supplied OVA 257-264 peptide for presentation to CD8+ Kb- restricted T lymphocytes. Thus contrary to current models of class I assembly in TAP-deficient RMA-S cells, the presumably 'empty' molecules are in fact associated with peptides at 26°C. Together, our data support the existence of an alternative mechanism of peptide binding and display by MHC class I molecules in TAP-deficient cells that could explain their ability to present Ag.

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