BACKGROUND The CD8 molecule is a cell surface glycoprotein that is expressed predominantly on class I MHC-restricted T cells. It is composed of a 36-kD alpha chain and a 30-kD beta chain. CD8 is expressed as a disulfide-linked homodimer, the alpha-alpha; predominant form expressed on natural killer cells and intestinal gamma-delta; T cells, or as an alpha-beta heterodimer, the form found on most thymocytes and peripheral T cells.1
CD8 functions as a co-receptor for cytotoxic T lymphocytes (CTLs), interacting with a nonpolymorphic region of the major histocompatibility complex (MHC) class I a3 domain on antigen-presenting cells. The CD8 co-receptor can modulate CD8+ T cell function through its contributions to T cell receptor (TCR) binding and signaling.2 The CD8 alpha-beta co-receptor amplifies the CD8+ T cell response to peptide/MHC Class I complexes on antigen-presenting cells (APC) by at least four mechanisms. First, CD8 binding to nonpolymorphic regions of the MHC molecule and beta 2-microglobulin is thought to stabilize the interaction between the TCR and peptide/MHC complexes. Second, CD8 binding to the MHC augments TCR signaling via activation of p56lck and LAT. Third, CD8 is thought to induce the co-localization of receptor complex molecules onto lipid rafts. Fourth, CD8 induces a conformational change in CD3 that is necessary for signal transduction.3 Modulation of surface CD8 expression on naive and effector cells can therefore alter the threshold peptide/MHC levels required to trigger proliferation, cytokine production and target cell lysis,4 effectively “tuning” the T cell response.
1. Zhong L et al.: Acta Crystallogr Sect F Struct Biol Cryst Commun. 66:435-438, 2010.
2. Choksi S et al.: Nature Med. 4:30 –314, 1998.
3. Parnes JR: Adv Immunol. 44:265-311, 1989.
4. Xiao Z et al.: J. Exp. Med. 204: 2667-2677, 2007.
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