The CD8 alpha beta heterodimer is integral to the selection of the class I-restricted lineage in the thymus; however, the contribution of the CD8 beta chain to coreceptor function is poorly understood. To understand whether the CD8 beta membrane proximal stalk region played a role in coreceptor function, we substituted it with the corresponding sequence from the CD8 alpha polypeptide and expressed the hybrid molecule in transgenic mice in place of endogenous CD8 beta. Although the stalk-swapped CD8 beta was expressed on the cell surface as a disulfide-bonded heterodimer at equivalent levels of expression to an endogenous CD8 beta molecule, it failed to restore selection of CD8(+) class I MHC-restricted T cells and it altered the response of peripheral T cells. Thus, the stalk region of the CD8 beta polypeptide has an essential role in ensuring functionality of the CD8 alpha beta heterodimer and its replacement compromises the interaction of CD8 with peptide-MHC complexes. The Journal of Immunology, 2009, 182: 121-129.
|Number of pages||9|
|Journal||Journal of Immunology|
|Publication status||Published - 1 Jan 2009|