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T cell receptor antagonism interferes with MHC clustering and integrin patterning during immunological synapse formation
| Content Provider | Semantic Scholar |
|---|---|
| Author | Sumen, Cenk Dustin, Michael L. Davis, Mark M. |
| Copyright Year | 2004 |
| Abstract | T cell activation by nonself peptide-major histocompatibility complex (MHC) antigenic complexes can be blocked by particular sequence variants in a process termed T cell receptor antagonism. The inhibition mechanism is not understood, although such variants are encountered in viral infections and may aid immune evasion. Here, we study the effect of antagonist peptides on immunological synapse formation by T cells. This cellular communication process features early integrin engagement and T cell motility arrest, referred to as the "stop signal." We find that synapses formed on membranes presenting antagonist-agonist complexes display reduced MHC density, which leads to reduced T cell proliferation that is not overcome by the costimulatory ligands CD48 and B7-1. Most T cells fail to arrest and crawl slowly with a dense ICAM-1 crescent at the leading edge. Similar aberrant patterns of LFA-1/ICAM-1 engagement in live T-B couples correlate with reduced calcium flux and IL-2 secretion. Hence, antagonist peptides selectively disable MHC clustering and the stop signal, whereas LFA-1 valency up-regulation occurs normally. |
| Starting Page | 579 |
| Ending Page | 590 |
| Page Count | 12 |
| File Format | PDF HTM / HTML |
| PubMed reference number | 15314068v1 |
| Volume Number | 166 |
| Journal | The Journal of cell biology |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | CD48 antigen Cellular Phone Immune Evasion Ligands Major Histocompatibility Complex Synapses T-Lymphocyte Tissue membrane Virus Diseases cell motility immunological synapse formation release of sequestered calcium ion into cytoplasm statistical cluster synaptogenesis |
| Content Type | Text |
| Resource Type | Article |