International Immunology, Vol. 15, No. 3, pp. 331-339,
March 2003
© 2003 Japanese Society for Immunology
Class I HLA oligomerization at the surface of B cells is controlled by exogenous ß2-microglobulin: implications in activation of cytotoxic T lymphocytes
1 Cell Biophysical Research Group of the Hungarian Academy of Sciences and 2 Department of Biophysics and Cell Biology, University of Debrecen, Medical Faculty, 4012 Debrecen, Hungary 3 Department of Biology, The Johns Hopkins University, Baltimore, MD 21218, USA 4 Department of Molecular Biology, Max-Planck Institute for Biophysical Chemistry, 37077 Göttingen, Germany 5 Department of Immunology, Eötvös Lorand University, 1117 Budapest, Hungary
Correspondence to: J. Matkó, Department of Immunology, Eötvös Lorand University, Pázmány Péter sétány 1/C, 1117 Budapest, Hungary. E-mail: matko{at}cerberus.elte.hu
Transmitting editor: I. Pecht
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 ß2-microglobulin (ß2m) 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 ß2m 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 ß2m 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 ß2m levels are reported.
Keywords: ß2-microglobulin, cell-surface HLA cluster, cytotoxicity, fluorescence resonance energy transfer, free heavy chain, T cell activation
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