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.
Keywords: CD4, CD8, MHC, T cell receptor, structure, T cell activation
Citation: Li Y, Yin Y and Mariuzza RA (2013) Structural and biophysical insights into the role of CD4 and CD8 in T cell activation. Front. Immunol. 4:206. doi: 10.3389/fimmu.2013.00206
Received: 07 May 2013; Paper pending published: 30 May 2013;
Accepted: 08 July 2013; Published online: 22 July 2013.
Edited by:Bruno Laugel, Cardiff University, UK
Reviewed by:Paula Kavathas, Yale University, USA
Copyright: © 2013 Li, Yin and Mariuzza. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc.
*Correspondence: Roy A. Mariuzza, Institute for Bioscience and Biotechnology Research, University of Maryland, 9600 Gudelsky Drive, Rockville, MD 20850, USA e-mail: email@example.com