2xfx | pdb_00002xfx
cattle MHC class I N01301 presenting an 11mer from Theileria parva
Structural highlights
FunctionQ30291_BOVIN Involved in the presentation of foreign antigens to the immune system.[SAAS:SAAS00004076] Publication Abstract from PubMedT cell receptor (TCR) recognition of peptide-MHC class I (pMHC) complexes is a crucial event in the adaptive immune response to pathogens. Peptide epitopes often display a strong dominance hierarchy, resulting in focusing of the response on a limited number of the most dominant epitopes. Such T cell responses may be additionally restricted by particular MHC alleles in preference to others. We have studied this poorly understood phenomenon using Theileria parva, a protozoan parasite that causes an often fatal lymphoproliferative disease in cattle. Despite its antigenic complexity, CD8+ T cell responses induced by infection with the parasite show profound immunodominance, as exemplified by the Tp1(214-224) epitope presented by the common and functionally important MHC class I allele N*01301. We present a high-resolution crystal structure of this pMHC complex, demonstrating that the peptide is presented in a distinctive raised conformation. Functional studies using CD8+ T cell clones show that this impacts significantly on TCR recognition. The unconventional structure is generated by a hydrophobic ridge within the MHC peptide binding groove, found in a set of cattle MHC alleles. Extremely rare in all other species, this feature is seen in a small group of mouse MHC class I molecules. The data generated in this analysis contribute to our understanding of the structural basis for T cell-dependent immune responses, providing insight into what determines a highly immunogenic p-MHC complex, and hence can be of value in prediction of antigenic epitopes and vaccine design. MHC class I bound to an immunodominant Theileria parva epitope demonstrates unconventional presentation to T cell receptors.,Macdonald IK, Harkiolaki M, Hunt L, Connelley T, Carroll AV, MacHugh ND, Graham SP, Jones EY, Morrison WI, Flower DR, Ellis SA PLoS Pathog. 2010 Oct 14;6(10):e1001149. PMID:20976198[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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