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The human CD8? M-4 isoform dominant in effector memory T cells has distinct cytoplasmic motifs that confer unique properties.


ABSTRACT: The CD8 co-receptor influences T cell recognition and responses in both anti-tumor and anti-viral immunity. During evolution in the ancestor of humans and chimpanzees, the CD8B gene acquired two additional exons. As a result, in humans, there are four CD8? splice variants (M1 to M4) that differ in their cytoplasmic tails. The M-1 isoform which is the equivalent of murine CD8?, is predominantly expressed in naïve T cells, whereas, the M-4 isoform is predominantly expressed in effector memory T cells. The characteristics of the M-4 isoform conferred by its unique 36 amino acid cytoplasmic tail are not known. In this study, we identified a dihydrophobic leucine-based receptor internalization motif in the cytoplasmic tail of M-4 that regulated its cell surface expression and downregulation after activation. Further the M-4 cytoplasmic tail was able to associate with ubiquitinated targets in 293T cells and mutations in the amino acids NPW, a potential EH domain binding site, either enhanced or inhibited the interaction. In addition, the M-4 tail was itself mono-ubiquitinated on a lysine residue in both 293T cells and a human T cell line. When peripheral blood human T cells expressed CD8?? M-4, the frequency of MIP-1? secreting cells responding to antigen presenting cells was two-fold higher as compared to CD8?? M-1 expressing T cells. Thus, the cytoplasmic tail of the CD8? M-4 isoform has unique characteristics, which likely contributed to its selective expression and function in human effector memory T cells.

SUBMITTER: Thakral D 

PROVIDER: S-EPMC3606432 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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The human CD8β M-4 isoform dominant in effector memory T cells has distinct cytoplasmic motifs that confer unique properties.

Thakral Deepshi D   Coman Maria M MM   Bandyopadhyay Arunima A   Martin Sunil S   Riley James L JL   Kavathas Paula B PB  

PloS one 20130322 3


The CD8 co-receptor influences T cell recognition and responses in both anti-tumor and anti-viral immunity. During evolution in the ancestor of humans and chimpanzees, the CD8B gene acquired two additional exons. As a result, in humans, there are four CD8β splice variants (M1 to M4) that differ in their cytoplasmic tails. The M-1 isoform which is the equivalent of murine CD8β, is predominantly expressed in naïve T cells, whereas, the M-4 isoform is predominantly expressed in effector memory T ce  ...[more]

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