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| | ==Crystal Structure of H2Kb-Q600V complex== | | ==Crystal Structure of H2Kb-Q600V complex== |
| - | <StructureSection load='4pv9' size='340' side='right' caption='[[4pv9]], [[Resolution|resolution]] 2.00Å' scene=''> | + | <StructureSection load='4pv9' size='340' side='right'caption='[[4pv9]], [[Resolution|resolution]] 2.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4pv9]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4PV9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4PV9 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4pv9]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4PV9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4PV9 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ABA:ALPHA-AMINOBUTYRIC+ACID'>ABA</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ABA:ALPHA-AMINOBUTYRIC+ACID'>ABA</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=4pv9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4pv9 OCA], [https://pdbe.org/4pv9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4pv9 RCSB], [https://www.ebi.ac.uk/pdbsum/4pv9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4pv9 ProSAT]</span></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2zsv|2zsv]], [[4pv8|4pv8]]</td></tr>
| + | |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">H2-K1, H2-K ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice]), B2m ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr>
| + | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4pv9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4pv9 OCA], [http://pdbe.org/4pv9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4pv9 RCSB], [http://www.ebi.ac.uk/pdbsum/4pv9 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4pv9 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/HA1B_MOUSE HA1B_MOUSE]] Involved in the presentation of foreign antigens to the immune system. [[http://www.uniprot.org/uniprot/B2MG_MOUSE B2MG_MOUSE]] Component of the class I major histocompatibility complex (MHC). Involved in the presentation of peptide antigens to the immune system. | + | [https://www.uniprot.org/uniprot/HA1B_MOUSE HA1B_MOUSE] Involved in the presentation of foreign antigens to the immune system. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 4pv9" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 4pv9" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Beta-2 microglobulin 3D structures|Beta-2 microglobulin 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Large Structures]] |
| - | [[Category: Gras, S]] | + | [[Category: Mus musculus]] |
| - | [[Category: Rossjohn, J]] | + | [[Category: Gras S]] |
| - | [[Category: Twist, K A]] | + | [[Category: Rossjohn J]] |
| - | [[Category: Cd8 t cell]]
| + | [[Category: Twist K-A]] |
| - | [[Category: Coronavirus]]
| + | |
| - | [[Category: H2kb]]
| + | |
| - | [[Category: Heteroclitic epitope]]
| + | |
| - | [[Category: Immune system]]
| + | |
| - | [[Category: T cell]]
| + | |
| - | [[Category: Tcr]]
| + | |
| Structural highlights
Function
HA1B_MOUSE Involved in the presentation of foreign antigens to the immune system.
Publication Abstract from PubMed
Peptides that bind poorly to MHC class I molecules often elicit low-functional avidity T cell responses. Peptide modification by altering the anchor residue facilitates increased binding affinity and may elicit T cells with increased functional avidity toward the native epitope ("heteroclitic"). This augmented MHC binding is likely to increase the half-life and surface density of the heteroclitic complex, but precisely how this enhanced T cell response occurs in vivo is not known. Furthermore, the ideal heteroclitic epitope will elicit T cell responses that completely cross-react with the native epitope, maximizing protection and minimizing undesirable off-target effects. Such epitopes have been difficult to identify. In this study, using mice infected with a murine coronavirus that encodes epitopes that elicit high (S510, CSLWNGPHL)- and low (S598, RCQIFANI)-functional avidity responses, we show that increased expression of peptide S598 but not S510 generated T cells with enhanced functional avidity. Thus, immune responses can be augmented toward T cell epitopes with low functional avidity by increasing Ag density. We also identified a heteroclitic epitope (RCVIFANI) that elicited a T cell response with nearly complete cross-reactivity with native epitope and demonstrated increased MHC/peptide abundance compared with native S598. Structural and thermal melt analyses indicated that the Q600V substitution enhanced stability of the peptide/MHC complex without greatly altering the antigenic surface, resulting in highly cross-reactive T cell responses. Our data highlight that increased peptide/MHC complex display contributes to heteroclitic epitope efficacy and describe parameters for maximizing immune responses that cross-react with the native epitope.
Structural and functional correlates of enhanced antiviral immunity generated by heteroclitic CD8 T cell epitopes.,Trujillo JA, Gras S, Twist KA, Croft NP, Channappanavar R, Rossjohn J, Purcell AW, Perlman S J Immunol. 2014 Jun 1;192(11):5245-56. doi: 10.4049/jimmunol.1400111. Epub 2014, May 2. PMID:24795457[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Trujillo JA, Gras S, Twist KA, Croft NP, Channappanavar R, Rossjohn J, Purcell AW, Perlman S. Structural and functional correlates of enhanced antiviral immunity generated by heteroclitic CD8 T cell epitopes. J Immunol. 2014 Jun 1;192(11):5245-56. doi: 10.4049/jimmunol.1400111. Epub 2014, May 2. PMID:24795457 doi:http://dx.doi.org/10.4049/jimmunol.1400111
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