Title: Differential Expression of Human CD8 Beta‐chain Isoforms and Regulation of M‐2 Isoform (splice variant 1) by Ubiquitination
Abstract: CD8αβ functions as a critical co-receptor with the T cell receptor. In contrast to the murine gene, the human CD8B gene encodes alternatively spliced variants with different cytoplasmic tails (M-1, M-2, M-3 and M-4). By quantitative RT-PCR we demonstrate differential mRNA expression patterns of these splice variants in resting, memory, and activated primary human CD8+ T cells. The mRNA pattern in total CD8+ T cells was generally M-1≥M-4≥M-2>M-3. The M-4 isoform was predominant in effector memory CD8+ T cells. After 24 hrs stimulation of CD8+ T cells the M-2 isoform mRNA levels were elevated 10–20 fold relative to resting cells in contrast to the other isoforms. Curiously, the M-2 isoform was not expressed on the cell surface in transfected cell lines. Using fluorescent chimeras of the extracellular domain of mouse CD8β fused to the cytoplasmic tails of each isoform in OT-1 hybridomas, the M-2 isoform was localized in lysosomal compartment regulated by ubiquitination of a lysine residue (K215) in the cytoplasmic tail. Upon short-term stimulation the M-2 protein localized to the cell surface with the TCR complex. Therefore, activated CD8+T cells exhibit an ability to modulate properties of CD8β by (a) altering the mRNA levels of an alternatively spliced transmembrane receptor M-2 and (b) altering trafficking and surface expression of M-2 through differential regulation by ubiquitination. Support by NIH RO1CA485011.
Publication Year: 2008
Publication Date: 2008-04-01
Language: en
Type: article
Indexed In: ['crossref']
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