Open AccessAn Essential Role for the Stalk Region of CD8β in the Coreceptor Function of CD8
Author(s) -
Lorna Rettig,
Louise McNeill,
Nitza Sarner,
Philippe Guillaume,
Immanuel F. Luescher,
Mauro Tolaini,
Dimitris Kioussis,
Rose Zamoyska
Publication year - 2009
Publication title -
the journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.737
H-Index - 372
eISSN - 1550-6606
pISSN - 0022-1767
DOI - 10.4049/jimmunol.182.1.121
Subject(s) - cd8 , stalk , microbiology and biotechnology , mhc class i , function (biology) , biology , lineage (genetic) , cytotoxic t cell , transgene , peptide , negative selection , chemistry , gene , biochemistry , antigen , genetics , in vitro , genome , horticulture
The CD8alphabeta heterodimer is integral to the selection of the class I-restricted lineage in the thymus; however, the contribution of the CD8beta chain to coreceptor function is poorly understood. To understand whether the CD8beta membrane proximal stalk region played a role in coreceptor function, we substituted it with the corresponding sequence from the CD8alpha polypeptide and expressed the hybrid molecule in transgenic mice in place of endogenous CD8beta. Although the stalk-swapped CD8beta was expressed on the cell surface as a disulfide-bonded heterodimer at equivalent levels of expression to an endogenous CD8beta 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 CD8beta polypeptide has an essential role in ensuring functionality of the CD8alphabeta heterodimer and its replacement compromises the interaction of CD8 with peptide-MHC complexes.
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