CD8 raft localization is induced by its assembly into CD8αβ heterodimers, not CD8αα homodimers

Abstract

The coreceptor CD8 is expressed as a CD8αβ heterodimer on major histocompatibility complex class I-restricted TCRαβ T cells, and as a CD8αα homodimer on subsets of memory T cells, intraepithelial lymphocytes, natural killer cells, and dendritic cells. Although the role of CD8αα is not well understood, it is increasingly clear that this protein is not a functional homologue of CD8αβ. On major histocompatibility complex class I-restricted T cells, CD8αβ is a more efficient TCR coreceptor than CD8αα. This property has for the mouse protein been attributed to the recruitment of CD8αβ into lipid rafts, which is dependent on CD8β palmitoylation. Here, these divergent distributions of CD8αβ and CD8αα are demonstrated for the human CD8 proteins as well. However, although palmitoylation of both CD8α and CD8β chains was detected, this modification did not contribute to raft localization. In contrast, arginines in the cytoplasmic domain are crucial for raft localization of CD8ββ. Most strikingly, the assembly of a non-raft localized CD8β chain with a non-raft localized CD8α chain resulted in raft-localized CD8αβ heterodimers. Using chimeric CD8 proteins, this property of the heterodimer was found to be determined by the assembly of CD8α and CD8β extracellular regions. The presence of two CD8α extracellular regions, on the other hand, appears to preclude raft localization. Thus, heterodimer formation and raft association are intimately linked for CD8αβ. These results emphasize that lipid raft localization is a key feature of human CD8αβ that clearly distinguishes it from CD8αα. © 2007 by The American Society for Biochemistry and Molecular Biology, Inc.