Class I HLA oligomerization at the surface of B cells is controlled by exogenous β2-microglobulin

Implications in activation of cytotoxic T lymphocytes

Andrea Bodnár, Zsolt Bacsó, Attila Jenei, Thomas M. Jovin, Michael A Edidin, Sándor Damjanovich, János Matkó

Research output: Contribution to journalArticle

Abstract

Submicroscopic molecular clusters (oligomers) of class I HLA have been detected by physical techniques [e.g. fluorescence resonance energy transfer (FRET) and single particle tracking of molecular diffusion] at the surface of various activated and transformed human cells, including B lymphocytes. Here, the sensitivity of this homotypic association to exogenous β2-microglobulin (β2m) and the role of free heavy chains (FHC) in class I HLA oligomerization were investigated on a B lymphoblastoid cell line, JY. Scanning near-field optical microscopy and FRET data both demonstrated that FHC and class I HLA heterodimers are co-clustered at the cell surface. Culturing the cells with excess β2m resulted in a reduced co-clustering and decreased molecular homotypic association, as assessed by FRET. The decreased HLA clustering on JY target cells (antigen-presenting cells) was accompanied with their reduced susceptibility to specific lysis by allospecific CD8+ cytotoxic T lymphocytes (CTL). JY B cells with reduced HLA clustering also provoked significantly weaker T cell activation signals, such as lower expression of CD69 activation marker and lower magnitude of TCR down-regulation, than did the untreated B cells. These results together suggest that the actual level of β2m available at the cell surface can control CTL activation and the subsequent cytotoxic effector function through regulation of the homotypic HLA-I association. This might be especially important in some inflammatory and autoimmune diseases where elevated serum β2m levels are reported.

Original languageEnglish (US)
Pages (from-to)331-339
Number of pages9
JournalInternational Immunology
Volume15
Issue number3
DOIs
StatePublished - Mar 1 2003

Fingerprint

Cytotoxic T-Lymphocytes
B-Lymphocytes
Fluorescence Resonance Energy Transfer
Cluster Analysis
Antigen-Presenting Cells
Lymphocyte Activation
Autoimmune Diseases
Microscopy
Down-Regulation
T-Lymphocytes
Cell Line
Serum

Keywords

  • β-microglobulin
  • Cell-surface HLA cluster
  • Cytotoxicity
  • Flourescence resonance energy transfer
  • Free heavy chain
  • T cell activation

ASJC Scopus subject areas

  • Immunology

Cite this

Class I HLA oligomerization at the surface of B cells is controlled by exogenous β2-microglobulin : Implications in activation of cytotoxic T lymphocytes. / Bodnár, Andrea; Bacsó, Zsolt; Jenei, Attila; Jovin, Thomas M.; Edidin, Michael A; Damjanovich, Sándor; Matkó, János.

In: International Immunology, Vol. 15, No. 3, 01.03.2003, p. 331-339.

Research output: Contribution to journalArticle

Bodnár, Andrea ; Bacsó, Zsolt ; Jenei, Attila ; Jovin, Thomas M. ; Edidin, Michael A ; Damjanovich, Sándor ; Matkó, János. / Class I HLA oligomerization at the surface of B cells is controlled by exogenous β2-microglobulin : Implications in activation of cytotoxic T lymphocytes. In: International Immunology. 2003 ; Vol. 15, No. 3. pp. 331-339.
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