Abstract
The interaction of T-cell receptors (TCRs) with self- and non-self-peptides in the major histocompatibility complex (MHC) stimulates crucial signaling events, which in turn can activate T lymphocytes. A variety of accessory molecules further modulate T-cell signaling. Of these, the CD4 and CD8 coreceptors make the most critical contributions to T cell sensitivity in vivo. Whereas, CD4 function in T cell development is well-characterized, its role in peripheral T cells remains incompletely understood. It was originally suggested that CD4 stabilizes weak interactions between TCRs and peptides in the MHC and delivers Lck kinases to that complex. The results of numerous experiments support the latter role, indicating that the CD4-Lck complex accelerates TCR-triggered signaling and controls the availability of the kinase for TCR in the absence of the ligand. On the other hand, extremely low affinity of CD4 for MHC rules out its ability to stabilize the receptor-ligand complex. In this review, we summarize the current knowledge on CD4 in T cells, with a special emphasis on the spatio-temporal organization of early signaling events and the relevance for CD4 function. We further highlight the capacity of CD4 to interact with the MHC in the absence of TCR. It drives the adhesion of T cells to the cells that express the MHC. This process is facilitated by the CD4 accumulation in the tips of microvilli on the surface of unstimulated T cells. Based on these observations, we suggest an alternative model of CD4 role in T-cell activation.
Highlights
T lymphocytes ( called T cells) continuously scan tissues for foreign antigens
In vertebrates, T lymphocytes continuously scan tissues for foreign antigens
Two models of CD4 function in peripheral T cells were suggested: 1) CD4 stabilizes the ternary complex of pMHC-T-cell receptors (TCRs) [Model 1; Figure 3 [46]], and 2) CD4 recruits Lck kinase to the proximity of the TCR/CD3 complex in order to phosphorylate the immunoreceptor tyrosine-based activation motifs (ITAMs) of CD3 molecules and initiate intracellular signaling during antigen-induced T cell activation [Model 2; Figure 3; [46, 60,61,62]]
Summary
T lymphocytes ( called T cells) continuously scan tissues for foreign antigens. TCRs are heterodimers formed by the subunits α and β, each of which contains two extracellular immunoglobulin (Ig)like domains, a single transmembrane domain and a short intracellular tail that lacks any known structural or functional motif (Figure 1). Based on the current understanding of these processes, it is predicted that the interaction between TCRs and the pMHC is the first step toward antigen-induced T-cell activation.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
