View source for 8roo


==Crystal structure of HLA B*18:01 in complex with YERMCNIL, an 8-mer epitope from Influenza A==
<StructureSection load='8roo' size='340' side='right'caption='[[8roo]], [[Resolution|resolution]] 1.40&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8roo]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Influenza_A_virus_(A/X-31(H3N2)) Influenza A virus (A/X-31(H3N2))]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8ROO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8ROO FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.4&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NO3:NITRATE+ION'>NO3</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8roo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8roo OCA], [https://pdbe.org/8roo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8roo RCSB], [https://www.ebi.ac.uk/pdbsum/8roo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8roo ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/S6AU73_HUMAN S6AU73_HUMAN] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
OBJECTIVES: Seasonal influenza viruses cause roughly 650 000 deaths annually despite available vaccines. CD8(+) T cells typically recognise influenza-derived peptides from internal structural and non-structural influenza proteins and are an attractive avenue for future vaccine design as they could reduce the severity of disease following infection with diverse influenza strains. CD8(+) T cells recognise peptides presented by the highly polymorphic Human Leukocyte Antigens class I molecules (HLA-I). Each HLA-I variant has distinct peptide binding preferences, representing a significant obstacle for designing vaccines that elicit CD8(+) T cell responses across broad populations. Consequently, the rational design of a CD8(+) T cell-mediated vaccine would require the identification of highly immunogenic peptides restricted to a range of different HLA molecules. METHODS: Here, we assessed the immunogenicity of six recently published novel influenza-derived peptides identified by mass-spectrometry and predicted to bind to the prevalent HLA-B*18:01 molecule. RESULTS: Using CD8(+) T cell activation assays and protein biochemistry, we showed that 3/6 of the novel peptides were immunogenic in several HLA-B*18:01(+) individuals and confirmed their HLA-B*18:01 restriction. We subsequently compared CD8(+) T cell responses towards the previously identified highly immunogenic HLA-B*18:01-restricted NP(219) peptide. Using X-ray crystallography, we solved the first crystal structures of HLA-B*18:01 presenting immunogenic influenza-derived peptides. Finally, we dissected the first TCR repertoires specific for HLA-B*18:01 restricted pathogen-derived peptides, identifying private and restricted repertoires against each of the four peptides. CONCLUSION: Overall the characterisation of these novel immunogenic peptides provides additional HLA-B*18:01-restricted vaccine targets derived from the Matrix protein 1 and potentially the non-structural protein and the RNA polymerase catalytic subunit of influenza viruses.

Characterisation of novel influenza-derived HLA-B*18:01-restricted epitopes.,Leong SL, Murdolo L, Maddumage JC, Koutsakos M, Kedzierska K, Purcell AW, Gras S, Grant EJ Clin Transl Immunology. 2024 May 10;13(5):e1509. doi: 10.1002/cti2.1509. , eCollection 2024. PMID:38737448<ref>PMID:38737448</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8roo" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Gras S]]
[[Category: Maddumage JC]]
[[Category: Murdolo LD]]