Human CD8β, But Not Mouse CD8β, Can Be Expressed in the Absence of CD8α as a ββ Homodimer1

The T cell coreceptor CD8 exists on mature T cells as disulfide-linked homodimers of CD8α polypeptide chains and heterodimers of CD8α- and CD8β-chains. The function of the CD8α-chain for binding to MHC class I and associating with the tyrosine kinase p56lck was demonstrated with CD8αα homodimers. CD8αβ functions as a better coreceptor, but the actual function of CD8β is less clear. Addressing this issue has been hampered by the apparent inability of CD8β to be expressed without CD8α. This study demonstrates that human, but not mouse, CD8β can be expressed on the cell surface without CD8α in both transfected COS-7 cells and murine lymphocytes. By creating chimeric proteins, we show that the murine Ig domain of CD8β is responsible for the lack of expression of murine CD8ββ dimers. In contrast to CD8αα, CD8ββ is unable to bind MHC class I in a cell-cell adhesion assay. Detection of this form of CD8 should facilitate studies on the function of the CD8 β-chain and indicates that caution should be used when interpreting studies on CD8 function using chimeric protein with the murine CD8ββ Ig domain. In addition, we demonstrate that the Ig domains of CD8α are also involved in controlling the ability of CD8 to be expressed. Mutation of B- and F-strand cysteine residues in CD8α reduced the ability of the protein to fold properly and, therefore, to be expressed.

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