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The ability of T cell receptors (TCR) to discriminate foreign from self-peptides presented by major histocompatibility complex (MHC) class II molecules is essential for an effective adaptive immune response. TCR recognition of self-peptides has been linked to autoimmune disease. Mutant self-peptides have been associated with tumors. Engagement of TCRs by a family of bacterial toxins know as superantigens has been responsible for toxic shock syndrome. Autoantibodies to V beta segments of T cell receptors have been isolated from patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). The autoantibodies block TH1-mediated inflammatory autodestructive reactions and are believed to be a method by which the immune system compensates for disease (ref5). T Cell and TCR Diversity Most human T cells express the TCR alpha-beta and either CD4 or CD8 molecule (single positive, SP). A small number of T cells lack both CD4 and CD8 (double negative, DN). Increased percentages of alpha-beta DN T cells have been identified in some autoimmune and immunodeficiency disorders. Gamma-delta T cells are primarily found within the epithelium. They show less TCR diversity and recognize antigens differently than alpha-beta T cells. Subsets of gamma-delta T cells have shown antitumor and immunoregulatory activity.
Programmed death receptor ligand 1 (PD-L1, also called B7-H1) is a recently described B7 family member. To date, one specific receptor has been identified that can be ligated by PD-L1. This receptor, programmed death receptor 1 (PD-1), has been shown to negatively regulate T-cell receptor (TCR) signaling. Upon ligating its receptor, PD-L1 has been reported to decrease TCR-mediated proliferation and cytokine production. PD-L1 expression was found to be abundant on many murine and human cancers and could be further up-regulated upon IFN-gamma stimulation. Thus, PD-L1 might play an important role in tumor immune evasion.
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