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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, 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. doi:10.1002/eji.200636765 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, Engineering and Medicine > Science > Mathematics | ||||
| Journal or Publication Title: | European Journal of Immunology | ||||
| Publisher: | Wiley - V C H Verlag GmbH & Co. KGaA | ||||
| ISSN: | 0014-2980 | ||||
| Official Date: | May 2007 | ||||
| Dates: |
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| Volume: | Vol.37 | ||||
| Number: | No.5 | ||||
| Number of Pages: | 11 | ||||
| Page Range: | pp. 1323-1333 | ||||
| DOI: | 10.1002/eji.200636765 | ||||
| Status: | Peer Reviewed | ||||
| Publication Status: | Published | ||||
| Access rights to Published version: | Restricted or Subscription Access |
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