Self-reactive human CD4 T cell clones form unusual immunological synapses.
Recognition of self-peptide-MHC (pMHC) complexes by CD4 T cells plays an important role in the pathogenesis of many autoimmune diseases. We analyzed formation of immunological synapses (IS) in self-reactive T cell clones from patients with multiple sclerosis and type 1 diabetes. All self-reactive T...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
2012
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| _version_ | 1797071601591648256 |
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| author | Schubert, D Gordo, S Sabatino, J Vardhana, S Gagnon, E Sethi, D Seth, N Choudhuri, K Reijonen, H Nepom, G Evavold, B Dustin, M Wucherpfennig, K |
| author_facet | Schubert, D Gordo, S Sabatino, J Vardhana, S Gagnon, E Sethi, D Seth, N Choudhuri, K Reijonen, H Nepom, G Evavold, B Dustin, M Wucherpfennig, K |
| author_sort | Schubert, D |
| collection | OXFORD |
| description | Recognition of self-peptide-MHC (pMHC) complexes by CD4 T cells plays an important role in the pathogenesis of many autoimmune diseases. We analyzed formation of immunological synapses (IS) in self-reactive T cell clones from patients with multiple sclerosis and type 1 diabetes. All self-reactive T cells contained a large number of phosphorylated T cell receptor (TCR) microclusters, indicative of active TCR signaling. However, they showed little or no visible pMHC accumulation or transport of TCR-pMHC complexes into a central supramolecular activation cluster (cSMAC). In contrast, influenza-specific T cells accumulated large quantities of pMHC complexes in microclusters and a cSMAC, even when presented with 100-fold lower pMHC densities. The self-reactive T cells also maintained a high degree of motility, again in sharp contrast to virus-specific T cells. 2D affinity measurements of three of these self-reactive T cell clones demonstrated a normal off-rate but a slow on-rate of TCR binding to pMHC. These unusual IS features may facilitate escape from negative selection by self-reactive T cells encountering very small amounts of self-antigen in the thymus. However, these same features may enable acquisition of effector functions by self-reactive T cells encountering large amounts of self-antigen in the target organ of the autoimmune disease. |
| first_indexed | 2024-03-06T22:55:41Z |
| format | Journal article |
| id | oxford-uuid:60499c81-2370-4b95-a5c6-6d733bd8def1 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T22:55:41Z |
| publishDate | 2012 |
| record_format | dspace |
| spelling | oxford-uuid:60499c81-2370-4b95-a5c6-6d733bd8def12022-03-26T17:52:31ZSelf-reactive human CD4 T cell clones form unusual immunological synapses.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:60499c81-2370-4b95-a5c6-6d733bd8def1EnglishSymplectic Elements at Oxford2012Schubert, DGordo, SSabatino, JVardhana, SGagnon, ESethi, DSeth, NChoudhuri, KReijonen, HNepom, GEvavold, BDustin, MWucherpfennig, KRecognition of self-peptide-MHC (pMHC) complexes by CD4 T cells plays an important role in the pathogenesis of many autoimmune diseases. We analyzed formation of immunological synapses (IS) in self-reactive T cell clones from patients with multiple sclerosis and type 1 diabetes. All self-reactive T cells contained a large number of phosphorylated T cell receptor (TCR) microclusters, indicative of active TCR signaling. However, they showed little or no visible pMHC accumulation or transport of TCR-pMHC complexes into a central supramolecular activation cluster (cSMAC). In contrast, influenza-specific T cells accumulated large quantities of pMHC complexes in microclusters and a cSMAC, even when presented with 100-fold lower pMHC densities. The self-reactive T cells also maintained a high degree of motility, again in sharp contrast to virus-specific T cells. 2D affinity measurements of three of these self-reactive T cell clones demonstrated a normal off-rate but a slow on-rate of TCR binding to pMHC. These unusual IS features may facilitate escape from negative selection by self-reactive T cells encountering very small amounts of self-antigen in the thymus. However, these same features may enable acquisition of effector functions by self-reactive T cells encountering large amounts of self-antigen in the target organ of the autoimmune disease. |
| spellingShingle | Schubert, D Gordo, S Sabatino, J Vardhana, S Gagnon, E Sethi, D Seth, N Choudhuri, K Reijonen, H Nepom, G Evavold, B Dustin, M Wucherpfennig, K Self-reactive human CD4 T cell clones form unusual immunological synapses. |
| title | Self-reactive human CD4 T cell clones form unusual immunological synapses. |
| title_full | Self-reactive human CD4 T cell clones form unusual immunological synapses. |
| title_fullStr | Self-reactive human CD4 T cell clones form unusual immunological synapses. |
| title_full_unstemmed | Self-reactive human CD4 T cell clones form unusual immunological synapses. |
| title_short | Self-reactive human CD4 T cell clones form unusual immunological synapses. |
| title_sort | self reactive human cd4 t cell clones form unusual immunological synapses |
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