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Front Immunol. 2013 Jul 22;4:206. doi: 10.3389/fimmu.2013.00206. eCollection 2013.

Structural and biophysical insights into the role of CD4 and CD8 in T cell activation.

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W. M. Keck Laboratory for Structural Biology, Institute for Bioscience and Biotechnology Research, University of Maryland , Rockville, MD , USA ; Department of Cell Biology and Molecular Genetics, University of Maryland , College Park, MD , USA.


T cell receptors (TCRs) recognize peptides presented by MHC molecules (pMHC) on an antigen-presenting cell (APC) to discriminate foreign from self-antigens and initiate adaptive immune responses. In addition, T cell activation generally requires binding of this same pMHC to a CD4 or CD8 co-receptor, resulting in assembly of a TCR-pMHC-CD4 or TCR-pMHC-CD8 complex and recruitment of Lck via its association with the co-receptor. Here we review structural and biophysical studies of CD4 and CD8 interactions with MHC molecules and TCR-pMHC complexes. Crystal structures have been determined of CD8αα and CD8αβ in complex with MHC class I, of CD4 bound to MHC class II, and of a complete TCR-pMHC-CD4 ternary complex. Additionally, the binding of these co-receptors to pMHC and TCR-pMHC ligands has been investigated both in solution and in situ at the T cell-APC interface. Together, these studies have provided key insights into the role of CD4 and CD8 in T cell activation, and into how these co-receptors focus TCR on MHC to guide TCR docking on pMHC during thymic T cell selection.


CD4; CD8; MHC; T cell activation; T cell receptor; structure

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