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Crystallization and preliminary X-ray structural studies of a high-affinity CD8αα co-receptor to pMHC

Cole, David, Rizkallah, Pierre, Sami, Malkit, Lissin, Nikolai M., Gao, Feng, Bell, John I., Boulter, Jonathan M., Glick, Meir, Vuidepot, Anne-Lise, Jakobsen, Bent K. and Gao, George F. 2005. Crystallization and preliminary X-ray structural studies of a high-affinity CD8αα co-receptor to pMHC. Acta Crystallographica Section F: Structural Biology and Crystallization Communications 61 (3) , pp. 285-287. 10.1107/S1744309105002988

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The class I CD8 positive T-cell response is involved in a number of conditions in which artificial down-regulation and control would be therapeutically beneficial. Such conditions include a number of autoimmune diseases and graft rejection in transplant patients. Although the CD8 T-cell response is dominated by the TCR–pMHC interaction, activation of T cells is in most cases also dependent on a number of associated signalling molecules. Previous work has demonstrated the ability of one such molecule (CD8) to act as an antagonist to T-cell activation if added in soluble form. Therefore, a high-affinity mutant CD8 (haCD8) has been developed with the aim of developing a therapeutic immunosuppressor. In order to fully understand the nature of the haCD8 interaction, this protein was crystallized using the sitting-drop vapour-diffusion method. Single haCD8 crystals were cryocooled and used for data collection. These crystals belonged to space group P6422 (assumed by similarity to the wild type), with unit-cell parameters a = 101.08, c = 56.54 Å. VM calculations indicated one molecule per asymmetric unit. A 2 Å data set was collected and the structure is currently being determined using molecular replacement.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Systems Immunity Research Institute (SIURI)
Subjects: R Medicine > R Medicine (General)
Uncontrolled Keywords: CD8αα; high affinity; structure-based design; immunosuppressors.
Publisher: Wiley
ISSN: 1744-3091
Last Modified: 26 Oct 2017 11:40

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