Regulation of CD1 antigen-presenting complex stability

Artur N Odyniec, Duarte C Barral, Salil Garg, Raju V. V. Tatituri, Gurdyal S. Besra, Michael B Brenner

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

For major histocompatibility complex class I and II molecules, the binding of specific peptide antigens is essential for assembly and trafficking and is at the center of their quality control mechanism. However, the role of lipid antigen binding in stabilization and quality control of CD1 heavy chain (HC).beta(2)-microglobulin (beta(2)m) complexes is unclear. Furthermore, the distinct trafficking and loading routes of CD1 proteins take them from mildly acidic pH in early endososmal compartments (pH 6.0) to markedly acidic pH in lysosomes (pH 5.0) and back to neutral pH of the cell surface (pH 7.4). Here, we present evidence that the stability of each CD1 HC.beta(2)m complex is determined by the distinct pH optima identical to that of the intracellular compartments in which each CD1 isoform resides. Although stable at acidic endosomal pH, complexes are only stable at cell surface pH 7.4 when bound to specific lipid antigens. The proposed model outlines a quality control program that allows lipid exchange at low endosomal pH without dissociation of the CD1 HC.beta(2)m complex and then stabilizes the antigen-loaded complex at neutral pH at the cell surface.

Original languageEnglish
Pages (from-to)11937-47
Number of pages11
JournalJournal of Biological Chemistry
Volume285
Issue number16
DOIs
Publication statusPublished - 16 Apr 2010

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CD1 Antigens
beta 2-Microglobulin
Quality Control
Antigens
Lipids
Lysosomes
Major Histocompatibility Complex

Keywords

  • Animals
  • Antigen Presentation
  • Antigens, CD1
  • Cell Line
  • Cell Membrane
  • Endosomes
  • HeLa Cells
  • Histocompatibility Antigens Class I
  • Histocompatibility Antigens Class II
  • Humans
  • Hydrogen-Ion Concentration
  • Lysosomes
  • Mice
  • Multiprotein Complexes
  • Protein Isoforms
  • Protein Stability
  • Recombinant Proteins
  • Transfection
  • beta 2-Microglobulin
  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

Cite this

Odyniec, A. N., Barral, D. C., Garg, S., Tatituri, R. V. V., Besra, G. S., & Brenner, M. B. (2010). Regulation of CD1 antigen-presenting complex stability. Journal of Biological Chemistry, 285(16), 11937-47. https://doi.org/10.1074/jbc.M109.077933
Odyniec, Artur N ; Barral, Duarte C ; Garg, Salil ; Tatituri, Raju V. V. ; Besra, Gurdyal S. ; Brenner, Michael B. / Regulation of CD1 antigen-presenting complex stability. In: Journal of Biological Chemistry. 2010 ; Vol. 285, No. 16. pp. 11937-47.
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Odyniec, AN, Barral, DC, Garg, S, Tatituri, RVV, Besra, GS & Brenner, MB 2010, 'Regulation of CD1 antigen-presenting complex stability', Journal of Biological Chemistry, vol. 285, no. 16, pp. 11937-47. https://doi.org/10.1074/jbc.M109.077933

Regulation of CD1 antigen-presenting complex stability. / Odyniec, Artur N; Barral, Duarte C; Garg, Salil; Tatituri, Raju V. V.; Besra, Gurdyal S.; Brenner, Michael B.

In: Journal of Biological Chemistry, Vol. 285, No. 16, 16.04.2010, p. 11937-47.

Research output: Contribution to journalArticle

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T1 - Regulation of CD1 antigen-presenting complex stability

AU - Odyniec, Artur N

AU - Barral, Duarte C

AU - Garg, Salil

AU - Tatituri, Raju V. V.

AU - Besra, Gurdyal S.

AU - Brenner, Michael B

PY - 2010/4/16

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AB - For major histocompatibility complex class I and II molecules, the binding of specific peptide antigens is essential for assembly and trafficking and is at the center of their quality control mechanism. However, the role of lipid antigen binding in stabilization and quality control of CD1 heavy chain (HC).beta(2)-microglobulin (beta(2)m) complexes is unclear. Furthermore, the distinct trafficking and loading routes of CD1 proteins take them from mildly acidic pH in early endososmal compartments (pH 6.0) to markedly acidic pH in lysosomes (pH 5.0) and back to neutral pH of the cell surface (pH 7.4). Here, we present evidence that the stability of each CD1 HC.beta(2)m complex is determined by the distinct pH optima identical to that of the intracellular compartments in which each CD1 isoform resides. Although stable at acidic endosomal pH, complexes are only stable at cell surface pH 7.4 when bound to specific lipid antigens. The proposed model outlines a quality control program that allows lipid exchange at low endosomal pH without dissociation of the CD1 HC.beta(2)m complex and then stabilizes the antigen-loaded complex at neutral pH at the cell surface.

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KW - Histocompatibility Antigens Class II

KW - Humans

KW - Hydrogen-Ion Concentration

KW - Lysosomes

KW - Mice

KW - Multiprotein Complexes

KW - Protein Isoforms

KW - Protein Stability

KW - Recombinant Proteins

KW - Transfection

KW - beta 2-Microglobulin

KW - Journal Article

KW - Research Support, N.I.H., Extramural

KW - Research Support, Non-U.S. Gov't

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DO - 10.1074/jbc.M109.077933

M3 - Article

VL - 285

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JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 16

ER -

Odyniec AN, Barral DC, Garg S, Tatituri RVV, Besra GS, Brenner MB. Regulation of CD1 antigen-presenting complex stability. Journal of Biological Chemistry. 2010 Apr 16;285(16):11937-47. https://doi.org/10.1074/jbc.M109.077933