Conformational dynamics of the β2-microglobulin C terminal in the cell-membrane-anchored major histocompatibility complex type I

M. Massa, P. Mangione, P. Pignatti, M. Stoppini, G. Zanotti, P. Arcidiaco, G. Merlini, G. Ferri, V. Bellotti

Research output: Contribution to journalArticlepeer-review

Abstract

We have recently described an anti-β2-microglobulin (β2-m) monoclonal antibody (mAb 14H3) capable of recognizing the epitope 92-99 of the protein in the monomeric native state as well as in the fibrillar polymeric state, but not in the major histocompatibility complex type I (MHCI) anchored to the cell membrane. In the present study, we investigated the molecular basis for the inaccessibility of the C-terminal end of β2-m in the MHCI complex, and demonstrated that mAb 14H3 binds the soluble fraction of the MHCI complex with a K(d) of 0.3 μM. An interaction between the complex and the membrane protects β2-m from immunological recognition at the MHCI level. This protection from antibody recognition can be weakened by procedures such as heat shock or γ irradiation that perturb the membrane structure and commit the cell to the apoptotic pathway. mAb 14H3 can recognize MHCI in a transient state that most likely precedes β2-m shedding and may be proposed as a useful tool for dynamic analysis of MHCI conformational modifications.

Original languageEnglish
Pages (from-to)675-683
Number of pages9
JournalCellular and Molecular Life Sciences
Volume57
Issue number4
Publication statusPublished - 2000

Keywords

  • β-Microglobulin
  • Amyloidosis
  • Apoptosis
  • Major histocompatibility antigen type I
  • Monoclonal antibody

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Cell Biology

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