Dataset Information

CD8?? homodimers function as a coreceptor for KIR3DL1.

ABSTRACT: Cluster of differentiation 8 (CD8) is a cell surface glycoprotein, which is expressed as 2 forms, ?? homodimer or ?? heterodimer. Peptide-loaded major histocompatibility complex class I (pMHC-I) molecules are major ligands for both forms of CD8. CD8?? 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 CD8?? homodimers is largely unknown. While CD8?? heterodimer is expressed exclusively on CD8+ T cells, the CD8?? homodimer is present in subsets of T cells and human natural killer (NK) cells. Here, we report that the CD8?? homodimer functions as a coreceptor for KIR3DL1, an inhibitory receptor of NK cells that is specific for certain MHC-I allotypes. CD8?? 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 CD8?? homodimers regulate KIR3DL1+ NK cell education. Together, these findings reveal another dimension to the modulation of NK cell activity.

SUBMITTER: Geng J

PROVIDER: S-EPMC6731649 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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CD8αα homodimers function as a coreceptor for KIR3DL1.

Geng Jie J Raghavan Malini M

Proceedings of the National Academy of Sciences of the United States of America 20190816 36

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 CD ...[more]

PMID: 31420518

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Project description:Bw4 homozygosity in human leukocyte antigen class B alleles has been associated with a delayed acquired immunodeficiency syndrome (AIDS) development and better control of human immunodeficiency virus type 1 (HIV-1) viral load (VL) than Bw6 homozygosity. Efficient CD8 T cell and natural killer (NK) cell functions have been described to restrain HIV-1 replication. However, the role of KIR3DL1 expression on these cells was not assessed in Bw4-homozygous participants infected with HIV-1 CRF01_A/E subtype, currently the most prevalent subtype in China. Here, we found that the frequency of KIR3DL1-expressing CD8 T cells of individuals homozygous for Bw6 [1.53% (0-4.56%)] was associated with a higher VL set point (Spearman rs?=?0.59, P?=?0.019), but this frequency of KIR3DL1+CD8+ T cells [1.37% (0.04-6.14%)] was inversely correlated with CD4 T-cell count in individuals homozygous for Bw4 (rs?=?-0.59, P?=?0.011). Moreover, CD69 and Ki67 were more frequently expressed in KIR3DL1-CD8+ T cells in individuals homozygous for Bw4 than Bw6 (P?=?0.046 for CD69; P?=?0.044 for Ki67), although these molecules were less frequently expressed in KIR3DL1+CD8+ T cells than in KIR3DL1-CD8+ T cells in both groups (all P?<?0.05). KIR3DL1-CD8+ T cells have stronger p24-specific CD8+ T-cell responses secreting IFN-? and CD107a than KIR3DL1+CD8+ T cells in both groups (all P?<?0.05). Thus, KIR3DL1 expression on CD8 T cells were associated with the loss of multiple functions. Interestingly, CD69+NK cells lacking KIR3DL1 expression were inversely correlated with HIV-1 VL set point in Bw4-homozygous individuals (rs?=?-0.52, P?=?0.035). Therefore, KIR3DL1-CD8+ T cells with strong early activation and proliferation may, together with KIR3DL1-CD69+NK cells, play a protective role during acute/early HIV infection in individuals homozygous for Bw4. These findings highlight the superior functions of KIR3DL1-CD8+ T cells and KIR3DL1-CD69+NK cells being a potential factor contributing to delayed disease progression in the early stages of HIV-1 infection.

Dataset Information

CD8?? homodimers function as a coreceptor for KIR3DL1.

Publications

CD8αα homodimers function as a coreceptor for KIR3DL1.

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