Nature Immunology 7, 256 - 264 (2006)
Published online: 12 February 2006; | doi:10.1038/ni1312
Structural basis for a major histocompatibility complex class Ib–restricted T cell responseHilary L Hoare1, 5, Lucy C Sullivan2, 5, Gabriella Pietra3, 4, Craig S Clements1, Eleanor J Lee2, Lauren K Ely1, Travis Beddoe1, Michela Falco3, Lars Kjer-Nielsen2, Hugh H Reid1, James McCluskey2, Lorenzo Moretta3, 4, Jamie Rossjohn1
& Andrew G Brooks21
The Protein Crystallography Unit, Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton, Victoria 3800, Australia. 2
Department of Microbiology and Immunology, University of Melbourne, Parkville, Victoria 3010, Australia. 3
Istituto Giannina Gaslini, Genova, Italy. 4
Department of Experimental Medicine, University of Genova, Italy. 5
These authors contributed equally to this work.
Correspondence should be addressed to Jamie Rossjohn jamie.rossjohn@med.monash.edu.au or Andrew G Brooks agbrooks@unimelb.edu.au In contrast to antigen-specific immunity orchestrated by major histocompatibility complex (MHC) class Ia molecules, the ancestrally related nonclassical MHC class Ib molecules generally mediate innate immune responses. Here we have demonstrated the structural basis by which the MHC class Ib molecule HLA-E mediates an adaptive MHC-restricted cytotoxic T lymphocyte response to human cytomegalovirus. Highly constrained by host genetics, the response showed notable fine specificity for position 8 of the viral peptide, which is the sole discriminator of self versus nonself. Despite the evolutionary divergence of MHC class Ia and class Ib molecules, the structure of the T cell receptor–MHC class Ib complex was very similar to that of conventional T cell receptor–MHC class Ia complexes. These results emphasize the evolutionary 'ambiguity' of HLA-E, which not only interacts with innate immune receptors but also has the functional capacity to mediate virus-specific cytotoxic T lymphocyte responses during adaptive immunity.
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