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| | {{STRUCTURE_1i1f| PDB=1i1f | SCENE= }} | | {{STRUCTURE_1i1f| PDB=1i1f | SCENE= }} |
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| - | '''CRYSTAL STRUCTURE OF HUMAN CLASS I MHC (HLA-A2.1) COMPLEXED WITH BETA 2-MICROGLOBULIN AND HIV-RT VARIANT PEPTIDE I1Y'''
| + | ===CRYSTAL STRUCTURE OF HUMAN CLASS I MHC (HLA-A2.1) COMPLEXED WITH BETA 2-MICROGLOBULIN AND HIV-RT VARIANT PEPTIDE I1Y=== |
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| - | ==Overview==
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| - | Designing altered peptide ligands to generate specific immunological reactivity when bound to class I major histocompatibility complexes is important for both therapeutic and prophylactic reasons. We have previously shown that two altered peptides, derived from human immunodeficiency virus (HIV)-reverse transcriptase (RT) residues 309-317, are more immunogenic in vitro than the wild-type peptide. One peptide variant, I1Y, was able to stimulate RT-specific cytotoxic T cells from the blood of three HIV-infected individuals better than the wild-type RT peptide. Both I1Y and I1F peptide variants increase the cell surface half-life of the peptide-class I complex approximately 3-fold over that of the RT peptide but have different immunological activities. These peptides are candidates for the design of vaccines for HIV due to their increased immunogenicity. To understand the basis for the increased cell surface stability compared with wild-type peptide and to understand the differences in T cell recognition between I1Y and I1F, we determined the x-ray crystal structures of the two class I MHC-peptide complexes. These structures indicate that the increased cell surface half-life is due to pi-pi stacking interactions between Trp-167 of HLA-A2.1 and the aromatic P1 residues of I1F and I1Y. Comparison of the structures and modeling potential T cell receptor (TCR) interactions suggests that T cell interactions and immunogenicity are different between I1Y and I1F for two reasons. First, subtle changes in the steric and polar properties of the I1Y peptide affect TCR engagement. Second, water-mediated hydrogen bond interactions between the P1-Tyr and the P4-Glu peptide residues increase peptide side chain rigidity of residues critical for TCR engagement.
| + | The line below this paragraph, {{ABSTRACT_PUBMED_10601290}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 10601290 is the PubMed ID number. |
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| | + | {{ABSTRACT_PUBMED_10601290}} |
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| | ==About this Structure== | | ==About this Structure== |
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| | [[Category: Hiv]] | | [[Category: Hiv]] |
| | [[Category: Human class i mhc]] | | [[Category: Human class i mhc]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 19:27:40 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 1 10:16:14 2008'' |
Revision as of 07:16, 1 July 2008
Template:STRUCTURE 1i1f
CRYSTAL STRUCTURE OF HUMAN CLASS I MHC (HLA-A2.1) COMPLEXED WITH BETA 2-MICROGLOBULIN AND HIV-RT VARIANT PEPTIDE I1Y
Template:ABSTRACT PUBMED 10601290
About this Structure
1I1F is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
The structural basis for the increased immunogenicity of two HIV-reverse transcriptase peptide variant/class I major histocompatibility complexes., Kirksey TJ, Pogue-Caley RR, Frelinger JA, Collins EJ, J Biol Chem. 1999 Dec 24;274(52):37259-64. PMID:10601290
Page seeded by OCA on Tue Jul 1 10:16:14 2008
