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CD28 antigen is a 44 kDa disulfide linked homodimeric T cell specific surface glycoprotein. CD28 is a cell adhesion molecule of the immunoglobulin superfamily which is constitutively expressed on most peripheral blood T lymphocytes. Moreover, CD28 is the critical T cell costimulatory receptor that provides the cell the important second activation signal by binding CD80 and CD86 which are expressed by antigen presenting cells. In addition to its co-stimulation role, CD28 functions by preventing T cells from entering an anergic-hyporesponsive state or from undergoing premature apoptotic cell death. In murine peripheral lymphoid organs and in the blood, all CD4+ and CD8+ T cells express CD28. In the thymus, CD28 expression is highest on immature CD3-, CD8+ and CD4+8+ cells, and on CD4-8- cells that express alpha/beta and gamma/delta TCR. The level of CD28 on mature CD4+ and CD8+ alpha/beta TCR+ thymocytes is two- to fourfold lower than on the immature cells. Diseases associated with CD28 dysfunction include mycosis fungiodes and Sezary's Disease.
EGFR, epidermal growth factor receptor, is a receptor tyrosine kinases that signals in response to various growth factors. Overexpression has been linked to numerous types of cancer and EGFR is the target of both biological and small molecular therapeutics. EGFR is encoded by the EGFR gene located on chromosome 7 in humans. EGFR belongs to the HER/ERbB family of proteins that includes three other receptor tyrosine kinases, ERbB2, ERbB3, ERbB4. EGFR is a transmembrane receptor and binding of its cognate ligands such as EGF (Epidermal Growth Factor) and TGF alpha (Transforming Growth Factor alpha) to the extracellular domain leads to EGFR dimerization followed by autophosphorylation of the tyrosine residues in the cytoplasmic domain. Overexpression is observed in tumors of the head and neck, brain, bladder, stomach, breast, lung, endometrium, cervix, vulva, ovary, esophagus, stomach and in squamous cell carcinoma.
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