HLA-B and HLA-C differ in their nanoscale organization at cell surfaces
| Autor: | Kennedy, PR, Barthen, C, Williamson, DJ, Davis, DM |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
EXPRESSION
HLA-B HLA-C Immunological Synapses Immunology INHIBITION Fluorescent Antibody Technique Gene Expression super-resolution HLA-C Antigens IMMUNITY CLASS-I PROTEINS ESCAPE RECEPTOR NANOCLUSTERS Humans NK cell Amino Acid Sequence Cysteine membrane Original Research GAG B-Lymphocytes Science & Technology COMPLEX MUTATIONS TRANSMEMBRANE SEQUENCE Cell Membrane immune synapse HLA class I nanoscale Killer Cells Natural HLA-B Antigens Life Sciences & Biomedicine Protein Binding |
| Zdroj: | Kennedy, P, Barthen, C, Williamson, D & Davis, D M 2019, ' HLA-B and HLA-C differ in their nanoscale organization at cell surfaces ', Frontiers in Immunology . https://doi.org/10.3389/fimmu.2019.00061 Frontiers in Immunology |
| DOI: | 10.3389/fimmu.2019.00061 |
| Popis: | The particular HLA class I variants an individual carries influences their resistance and susceptibility to a multitude of diseases. Expression level and variation in the peptide binding region correlates with, for example, a person's progression to AIDS after HIV infection. One factor which has not yet been addressed is whether or not different HLA class I proteins organize differently in the cell membrane on a nanoscale. Here, we examined the organization of three HLA-B allotypes (B*2705, B*5301, and B*5701) and two HLA-C allotypes (C*0602 and C*0702) in the membrane of 721.221 cells which otherwise lack expression of HLA-B or HLA-C. All these allotypes are ligands for the T cell receptor and leukocyte immunoglobulin-like receptors, but additionally, the HLA-B allotypes are ligands for the killer-cell immunoglobulin-like receptor family member KIR3DL1, HLA-C*0602 is a ligand for KIR2DL1, and HLA-C*0702 is a ligand for KIR2DL2/3. Using super-resolution microscopy, we found that both HLA-B and HLA-C formed more clusters and a greater proportion of HLA contributed to clusters, when expressed at lower levels. Thus, HLA class I organization is a covariate in genetic association studies of HLA class I expression level with disease progression. Surprisingly, we also found that HLA-C was more clustered than HLA-B when expression level was controlled. HLA-C consistently formed larger and more numerous clusters than HLA-B and a greater proportion of HLA-C contributed to clusters than for HLA-B. We also found that the organization of HLA class I proteins varied with cell type. T cells exhibited a particularly clustered organization of HLA class I while B cells expressed a more uniform distribution. In summary, HLA class I variants are organized differently in the cell surface membrane which may impact their functions. |
| Databáze: | OpenAIRE |
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