CD8αα homodimers function as a coreceptor for KIR3DL1

Abstract

Cluster of differentiation 8 (CD8) is a cell surface glycoprotein, which is expressed as 2 forms, αα homodimer or αβ heterodimer. Peptide-loaded major histocompatibility complex class I (pMHC-I) molecules are major ligands for both forms of CD8. CD8αβ is a coreceptor for the T cell receptor (TCR) and binds to the same cognate pMHC-I as the TCR, thus enabling or augmenting T cell responses. The function of CD8αα homodimers is largely unknown. While CD8αβ heterodimer is expressed exclusively on CD8+ T cells, the CD8αα homodimer is present in subsets of T cells and human natural killer (NK) cells. Here, we report that the CD8αα homodimer functions as a coreceptor for KIR3DL1, an inhibitory receptor of NK cells that is specific for certain MHC-I allotypes. CD8αα enhances binding of pMHC-I to KIR3DL1, increases KIR3DL1 clustering at the immunological synapse, and augments KIR3DL1-mediated inhibition of NK cell activation. Additionally, interactions between pMHC-I and CD8αα homodimers regulate KIR3DL1+ NK cell education. Together, these findings reveal another dimension to the modulation of NK cell activity.

An Anti-Tumor Vaccine Against Marek's Disease Virus Induces Differential Activation and Memory Response of γδ T Cells and CD8 T Cells in Chickens

“…In mammals, CD8 + T cells and γδ T cells or innate-like T cells can express two forms of CD8 coreceptor: CD8αα homodimer and CD8αβ heterodimer ( 40 ). We therefore examined the differential expression of these two coreceptors on chicken γδ T cells and CD8α + T cells (TCRγδ − CD3 + CD8α + ).…”

Intestinal intraepithelial lymphocytes: Maintainers of intestinal immune tolerance and regulators of intestinal immunity

“…90,91 In addition, CD8 is expressed not only by IELs but also by other cell lineages, such as subsets of human NK cells and dendritic cells. 89,92 Recent research shows that the CD8 homodimer also functions as a coreceptor for KIR3DL1 (an inhibitory receptor of NK cells ) and that this interaction augments KIR3DL1- and inhibitory receptors such as lymphocyte antigen 49 (Ly49A) and Ly49G2. 9 In newborn mice and humans, CD8 + TCR + IELs represent a polyclonal TCR repertoire, 10 but in mature mice and humans, TCR repertoire of these IELs becomes slightly oligoclonal, and the degree of oligoclonality is significantly higher in IELs than in peripheral lymph node T cells.…”

Impact of Early ARV Initiation on Relative Proportions of Effector and Regulatory CD8 T Cell in Mesenteric Lymph Nodes and Peripheral Blood During Acute SIV Infection of Rhesus Macaques

“…CD8αβ is a T-cell receptor (TCR) coreceptor which is essential for CD8 development and function, while the function of CD8αα is largely unknown. Differences in sensitivity to antigen, the efficiency of activation, and the stage of CD8 differentiation have been reported for each isoform ( 10 – 12 ). The αα homodimer is mainly expressed by terminal-differentiated CD8 T cells, a population with lower cytotoxicity capacity and poor antiviral response that is likely to be unable to control the viral replication.…”

“…The αα homodimer is mainly expressed by terminal-differentiated CD8 T cells, a population with lower cytotoxicity capacity and poor antiviral response that is likely to be unable to control the viral replication. At the same time, the αβ heterodimer has been associated with a more functional phenotype ( 10 – 12 ).…”