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Generation of Human Alloantigen-specific T Cells from Peripheral Blood
Published on: November 21, 2014
Human major histocompatibility molecules have the intrinsic ability to form homotypic associations
K Triantafilou1, M Triantafilou, K M Wilson
1Department of Biological Sciences, University of Essex, Colchester, United Kingdom. ktrian@essex.ac.uk
Insights
Major histocompatibility complex (MHC) class I and class II molecules, including HLA-DR and HLA-DQ, self-associate on antigen-presenting cells. These homotypic associations form stable dimers and multimers at the cell surface.
Area of Science:
- Immunology
- Molecular Biology
- Cell Biology
Background:
- Major histocompatibility complex (MHC) molecules play crucial roles in immune responses.
- Understanding the self-association patterns of MHC molecules is vital for comprehending immune cell interactions.
Purpose of the Study:
- To investigate the homotypic associations of MHC class I and class II molecules.
- To determine if these associations are stable and occur at the cell surface.
Main Methods:
- Immunoprecipitation using specific monoclonal antibodies (mAbs) like L243 (for HLA-DR) and W632 (for MHC class I).
- Analysis of cell extracts from labeled B cells and transfectant fibroblasts.
- Thermostability assays in SDS to assess the stability of molecular complexes.
Main Results:
- HLA-DR molecules form stable dimers of dimers and single heterodimers on B cells.
- HLA-DQ molecules also exhibit homotypic associations, forming similar structures.
- MHC class I molecules were found to exist as multimers (90 kDa and 135 kDa structures).
- Non-MHC molecules like CD14 did not show self-association under the same conditions.
Conclusions:
- MHC class I and class II molecules possess an intrinsic ability to form homotypic associations.
- These self-associations occur at the cell surface of antigen-presenting cells.
- The findings suggest a novel mechanism for regulating immune cell interactions via MHC molecule self-assembly.
Abstract:
We have investigated the homotypic associations of major histocompatibilty, class II and class I molecules using immunoprecipitation from detergent solubilised cell extracts. A 120-kDa structure corresponding to an HLA-DR dimer of dimers was immunoprecipitated by the HLA-DR specific mAb L243 from both biotinylated cell-surface and metabolically labeled B cells and transfectant fibroblasts. The thermostability of this structure in SDS was examined. It was detected at 4 degrees C, 22 degrees C, and 37 degrees C, but not at 50 degrees C or 100 degrees C. Experiments performed with L243 Fab fragments and with purified HLA-DR molecules, indicated the presence of HLA-DR dimers of dimers and single heterodimers on B cells. HLA-DQ was also found to form SDS-stable dimers of dimers and single heterodimers on the cell surface of B cells, demonstrating that HLA class II isotypes, other than HLA-DR, also form homotypic associations. Similar experiments performed with HLA class I specific mAb, W632, revealed the existence of a 90 kDa and a 135-kDa structure corresponding to a MHC class I multimers. Under the same conditions, non-MHC molecules such as CD14 were found not to self-associate. These findings indicate that major histocompatibility molecules have the intrinsic ability to form homotypic associations at the cell surface of antigen presenting cells.
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