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

• Published in: Frontiers in immunology Vol. 4; p. 206
• Main Authors: Li, Yili, Yin, Yiyuan, Mariuzza, Roy A
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 01.01.2013
• Subjects: CD4; CD8; Immunology; MHC; Structure; T cell activation; T cell receptor; MHC; CD4; T cell receptor; T cell activation; CD8; structure
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2013.00206

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.