An Essential Role for the Stalk Region of CD8 beta in the Coreceptor Function of CD8

Lorna Rettig, Louise McNeill, Nitza Sarner, Philippe Guillaume, Immanuel Luescher, Mauro Tolaini, Dimitris Kioussis, Rose Zamoyska

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)121-129
Number of pages9
JournalJournal of Immunology
Volume182
Issue number1
Publication statusPublished - 1 Jan 2009

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