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

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 naive 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.
Mesh Terms:
Blotting, Western, CD8 Antigens, Cell Line, Cells, Cultured, Chemokine CCL4, Cytoplasm, Flow Cytometry, Humans, Immunoprecipitation, Mutagenesis, Site-Directed, Protein Isoforms, Protein Structure, Tertiary
PLoS One
Date: Mar. 28, 2013
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