CD8αα and ‐αβ isotypes are equally recruited to the immunological synapse through their ability to bind to MHC class I

Abstract

Bimolecular fluorescence complementation was used to engineer CD8 molecules so that CD8aa and CD8ab dimers can be independently visualized on the surface of a T cell during antigen recognition. Using this approach, we show that CD8aa is recruited to the immunological synapse almost as well as CD8ab, but because the kinase Lck associates preferentially with CD8ab in lipid rafts, CD8aa is the weaker co-receptor. During recognition of the strong CD8aa ligand H2-TL, CD8aa is preferentially recruited. Thus, recruitment of the two CD8 species correlates with their relative binding to the available ligands, rather than with the co-receptor functions of the CD8 species.

A ternary complex comprising transportin1, Rab8 and the ciliary targeting signal directs proteins to ciliary membranes

“…CD8a–GFP×2 and CD8a–GFP×3 were essentially undetectable at cilia (), implying that the ciliary membrane diffusion barrier has a cytosolic size-exclusion limit of 50–100 kDa (considering that CD8a forms a homodimer; Rybakin et al, 2011), similar to the value observed for soluble proteins (Kee et al, 2012). …”

Coreceptor affinity for MHC defines peptide specificity requirements for TCR interaction with coagonist peptide–MHC

“…4, A and B), indicating that the TCR interaction with nonstimulatory pMHCI was at most a minor determinant of coagonism for OT-I T cells. We also noted that recruitment of CD8 to the immunological synapse (Yachi et al, 2005;Rybakin et al, 2011) was unperturbed by the sc-K b VSV-TCRm mutation (not depicted).…”

“…The CD8 coreceptor's interaction with nonstimulatory MHCI has been suggested to be important for coagonism in MHCI-restricted cells (Yachi et al, 2005;Gascoigne, 2008;Gascoigne et al, 2010). Nonstimulatory pMHC alone can recruit CD8 to the T cell-APC interface (Yachi et al, 2005;Rybakin et al, 2011). Also, coagonist pMHCs became antagonists in CD8-negative cells (Stone et al, 2011).…”

The molecular determinants of CD8 co‐receptor function

“…14,15 The signalling role of the CD8 a-chain can be enhanced by palmitoylation of the CD8 b-chain at a membrane-proximal cysteine. 16 Palmitoylation at this site allows the recruitment of the tripartite TCR-CD3-CD8 signalling complex to detergent-insoluble membrane domains, or lipid rafts. 17,18 Lipid rafts are made up of ordered microdomains, enriched with sphingolipids and cholesterol, that exclude molecules such as phosphatases (CD45) but recruit molecules that are critical for T-cell activation, such as p56 Lck and the linker for activation of T cells.…”

“…This interaction leads to a signalling cascade that recruits ZAP‐70 to the TCR–CD3 complex, leading to the amplification or enhancement of T‐cell activation signals . The signalling role of the CD8 α‐chain can be enhanced by palmitoylation of the CD8 β‐chain at a membrane‐proximal cysteine . Palmitoylation at this site allows the recruitment of the tripartite TCR–CD3–CD8 signalling complex to detergent‐insoluble membrane domains, or lipid rafts .…”