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Enhanced immunogenicity of CTL antigens through mutation of the CD8 binding MHC class I invariant region
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Wooldridge, Linda, Lissina, Anna, Vernazza, Jonathan, Gostick, Emma, Laugel, Bruno, Hutchinson, Sarah L., Mirza, Fareed, Dunbar, P. Rod, Boulter, Jonathan M., Glick, Meir, Cerundolo, Vincenzo, Berg, Hugo van den, 1968-, Price, David A. and Sewell, Andrew K.. (2007) Enhanced immunogenicity of CTL antigens through mutation of the CD8 binding MHC class I invariant region. European Journal of Immunology, Vol.37 (No.5). pp. 1323-1333. ISSN 0014-2980
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Official URL: http://dx.doi.org/10.1002/eji.200636765
Abstract
CD8(+) cytotoxic T lymphocytes (CTL) are key determinants of immunity to intracellular pathogens and neoplastic cells. Recognition of specific antigens in the form of peptide-MHC class I complexes (pMHCI) presented on the target cell surface is mediated by T cell receptor (TCR) engagement. The CD8 coreceptor binds to invariant domains of pMHCI and facilitates antigen recognition. Here, we investigate the biological effects of a Q115E substitution in the a2 domain of human leukocyte antigen (HLA)-A*0201 that enhances CD8 binding by, -50% without altering TCR/pMHCI interactions. Soluble and cell surface-expressed forms of Q115E HLA-A*0201 exhibit enhanced recognition by CTL without loss of specificity. These CD8-enhanced antigens induce greater CD3 chain phosphorylation in cognate CTL leading to substantial increases in cytokine production, proliferation and priming of naive T cells. This effect provides a fundamental new mechanism with which to. enhance cellular immunity to specific T cell antigens.
| Item Type: | Journal Article |
|---|---|
| Subjects: | Q Science > QR Microbiology > QR180 Immunology |
| Divisions: | Faculty of Science > Mathematics |
| Journal or Publication Title: | European Journal of Immunology |
| Publisher: | Wiley - V C H Verlag GmbH & Co. KGaA |
| ISSN: | 0014-2980 |
| Date: | May 2007 |
| Volume: | Vol.37 |
| Number: | No.5 |
| Number of Pages: | 11 |
| Page Range: | pp. 1323-1333 |
| Identification Number: | 10.1002/eji.200636765 |
| Status: | Peer Reviewed |
| Publication Status: | Published |
| Access rights to Published version: | Restricted or Subscription Access |
| URI: | http://wrap.warwick.ac.uk/id/eprint/31923 |
Data sourced from Thomson Reuters' Web of Knowledge
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