2h6p
From Proteopedia
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'''Crystal structure of HLA-B*3501 presenting the human cytochrome P450 derived peptide, KPIVVLHGY''' | '''Crystal structure of HLA-B*3501 presenting the human cytochrome P450 derived peptide, KPIVVLHGY''' | ||
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| + | ==Overview== | ||
| + | Our understanding of the molecular mechanisms of T cell alloreactivity remains limited by the lack of systems for which both the T cell receptor allo- and cognate ligand are known. Here we provide evidence that a single alloreactive T cell receptor interacts with analogous structural regions of its cognate ligand, HLA-B*0801(FLRGRAYGL), as its allogeneic ligand, HLA-B*3501(KPIVVLHGY). The crystal structures of the binary peptide-major histocompatibility complexes show marked differences in the conformation of the heavy chains as well as the bound peptides. Nevertheless, both epitopes possess a prominent solvent-exposed aromatic residue at position 7 flanked by a small glycine at position 8 of the peptide determinant. Moreover, regions of close structural homology between the heavy chains of HLA B8 and HLA B35 coincided with regions that have previously been implicated in "hot spots" of T cell receptor recognition. The avidity of this human T cell receptor was also comparable for the allo- and cognate ligand, consistent with the modes of T cell receptor binding being broadly similar for these complexes. Collectively, it appears that highly focused structural mimicry against a diverse structural background provides a basis for the observed alloreactivity in this system. This cross-reactivity underpins the T cell degeneracy inherent in the limited mature T cell repertoire that must respond to a vast diversity of microbial antigens. | ||
==About this Structure== | ==About this Structure== | ||
2H6P is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2H6P OCA]. | 2H6P is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2H6P OCA]. | ||
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| + | ==Reference== | ||
| + | Alloreactivity between disparate cognate and allogeneic pMHC-I complexes is the result of highly focused, peptide-dependent structural mimicry., Archbold JK, Macdonald WA, Miles JJ, Brennan RM, Kjer-Nielsen L, McCluskey J, Burrows SR, Rossjohn J, J Biol Chem. 2006 Nov 10;281(45):34324-32. Epub 2006 Sep 8. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16963442 16963442] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
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[[Category: Gene regulation]] | [[Category: Gene regulation]] | ||
[[Category: Immune system]] | [[Category: Immune system]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jun 4 09:57:53 2008'' |
Revision as of 06:57, 4 June 2008
Crystal structure of HLA-B*3501 presenting the human cytochrome P450 derived peptide, KPIVVLHGY
Overview
Our understanding of the molecular mechanisms of T cell alloreactivity remains limited by the lack of systems for which both the T cell receptor allo- and cognate ligand are known. Here we provide evidence that a single alloreactive T cell receptor interacts with analogous structural regions of its cognate ligand, HLA-B*0801(FLRGRAYGL), as its allogeneic ligand, HLA-B*3501(KPIVVLHGY). The crystal structures of the binary peptide-major histocompatibility complexes show marked differences in the conformation of the heavy chains as well as the bound peptides. Nevertheless, both epitopes possess a prominent solvent-exposed aromatic residue at position 7 flanked by a small glycine at position 8 of the peptide determinant. Moreover, regions of close structural homology between the heavy chains of HLA B8 and HLA B35 coincided with regions that have previously been implicated in "hot spots" of T cell receptor recognition. The avidity of this human T cell receptor was also comparable for the allo- and cognate ligand, consistent with the modes of T cell receptor binding being broadly similar for these complexes. Collectively, it appears that highly focused structural mimicry against a diverse structural background provides a basis for the observed alloreactivity in this system. This cross-reactivity underpins the T cell degeneracy inherent in the limited mature T cell repertoire that must respond to a vast diversity of microbial antigens.
About this Structure
2H6P is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Alloreactivity between disparate cognate and allogeneic pMHC-I complexes is the result of highly focused, peptide-dependent structural mimicry., Archbold JK, Macdonald WA, Miles JJ, Brennan RM, Kjer-Nielsen L, McCluskey J, Burrows SR, Rossjohn J, J Biol Chem. 2006 Nov 10;281(45):34324-32. Epub 2006 Sep 8. PMID:16963442 Page seeded by OCA on Wed Jun 4 09:57:53 2008
