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- Title
Unplugging the T cell receptor.
- Authors
Poli, Guido; Bordignon, Claudio
- Abstract
The T cell antigen receptor (TCR) is a multimeric complex composed of an antigenbinding αβ heterodimer and a signal-transducing complex consisting of the CD3 dimers and a TCR ς homodimer. Down-regulation of the ς chain prevents T cell activation and proliferation in response to cognate peptide bound to the major histocompatibility complex of antigenpresenting cells (APCs). Several pathological conditions, including chronic infections, certain tumors and autoimmune diseases have been linked to a down-regulation of the ς chain. This study also suggests that genetic engineering of T lymphocytes to constitutively express the ς chain may generate effector cells capable of effectively controlling pathogens that escape the immune system by inducing ς chain down-regulation. This idea is now being tested at the clinical level in patients infected with human immunodeficiency virus. Because tumors may also escape adaptive immunosurveillance through TCR ς chain down-regulation, T cells genetically engineered to constitutively express the ς chain should also be considered for immunotherapy of certain tumors.
- Subjects
T cell receptors; ONCOLOGY; MAJOR histocompatibility complex; IMMUNE system; AUTOIMMUNE diseases
- Publication
Nature Immunology, 2003, Vol 4, Issue 10, p943
- ISSN
1529-2908
- Publication type
Article
- DOI
10.1038/ni1003-943