5nq1: Difference between revisions
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==Porcine (Sus scrofa) Major Histocompatibility Complex, class I, with human beta2 micro globulin, presenting DFEREGYSL== | ==Porcine (Sus scrofa) Major Histocompatibility Complex, class I, with human beta2 micro globulin, presenting DFEREGYSL== | ||
<StructureSection load='5nq1' size='340' side='right' caption='[[5nq1]], [[Resolution|resolution]] 2.14Å' scene=''> | <StructureSection load='5nq1' size='340' side='right'caption='[[5nq1]], [[Resolution|resolution]] 2.14Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5nq1]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5NQ1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5NQ1 FirstGlance]. <br> | <table><tr><td colspan='2'>[[5nq1]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Pig Pig]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5NQ1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5NQ1 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5npz|5npz]], [[5nq0|5nq0]], [[5nq2|5nq2]], [[5nq3|5nq3]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5npz|5npz]], [[5nq0|5nq0]], [[5nq2|5nq2]], [[5nq3|5nq3]]</td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SLA-1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9823 PIG]), B2M, CDABP0092, HDCMA22P ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=5nq1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5nq1 OCA], [http://pdbe.org/5nq1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5nq1 RCSB], [http://www.ebi.ac.uk/pdbsum/5nq1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5nq1 ProSAT]</span></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=5nq1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5nq1 OCA], [http://pdbe.org/5nq1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5nq1 RCSB], [http://www.ebi.ac.uk/pdbsum/5nq1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5nq1 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
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== Function == | == Function == | ||
[[http://www.uniprot.org/uniprot/B1PJV3_PIG B1PJV3_PIG]] Involved in the presentation of foreign antigens to the immune system.[SAAS:SAAS00291881] [[http://www.uniprot.org/uniprot/B2MG_HUMAN B2MG_HUMAN]] Component of the class I major histocompatibility complex (MHC). Involved in the presentation of peptide antigens to the immune system. | [[http://www.uniprot.org/uniprot/B1PJV3_PIG B1PJV3_PIG]] Involved in the presentation of foreign antigens to the immune system.[SAAS:SAAS00291881] [[http://www.uniprot.org/uniprot/B2MG_HUMAN B2MG_HUMAN]] Component of the class I major histocompatibility complex (MHC). Involved in the presentation of peptide antigens to the immune system. | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
There is increasing evidence that induction of local immune responses is a key component of effective vaccines. For respiratory pathogens, for example tuberculosis and influenza, aerosol delivery is being actively explored as a method to administer vaccine antigens. Current animal models used to study respiratory pathogens suffer from anatomical disparity with humans. The pig is a natural and important host of influenza viruses and is physiologically more comparable to humans than other animal models in terms of size, respiratory tract biology and volume. It may also be an important vector in the birds to human infection cycle. A major drawback of the current pig model is the inability to analyze antigen-specific CD8+ T-cell responses, which are critical to respiratory immunity. Here we address this knowledge gap using an established in-bred pig model with a high degree of genetic identity between individuals, including the MHC (Swine Leukocyte Antigen (SLA)) locus. We developed a toolset that included long-term in vitro pig T-cell culture and cloning and identification of novel immunodominant influenza-derived T-cell epitopes. We also generated structures of the two SLA class I molecules found in these animals presenting the immunodominant epitopes. These structures allowed definition of the primary anchor points for epitopes in the SLA binding groove and established SLA binding motifs that were used to successfully predict other influenza-derived peptide sequences capable of stimulating T-cells. Peptide-SLA tetramers were constructed and used to track influenza-specific T-cells ex vivo in blood, the lungs and draining lymph nodes. Aerosol immunization with attenuated single cycle influenza viruses (S-FLU) induced large numbers of CD8+ T-cells specific for conserved NP peptides in the respiratory tract. Collectively, these data substantially increase the utility of pigs as an effective model for studying protective local cellular immunity against respiratory pathogens. | |||
Induction of influenza-specific local CD8 T-cells in the respiratory tract after aerosol delivery of vaccine antigen or virus in the Babraham inbred pig.,Tungatt K, Dolton G, Morgan SB, Attaf M, Fuller A, Whalley T, Hemmink JD, Porter E, Szomolay B, Montoya M, Hammond JA, Miles JJ, Cole DK, Townsend A, Bailey M, Rizkallah PJ, Charleston B, Tchilian E, Sewell AK PLoS Pathog. 2018 May 17;14(5):e1007017. doi: 10.1371/journal.ppat.1007017., eCollection 2018 May. PMID:29772011<ref>PMID:29772011</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 5nq1" 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: Human]] | |||
[[Category: Large Structures]] | |||
[[Category: Pig]] | |||
[[Category: Rizkallah, P J]] | [[Category: Rizkallah, P J]] | ||
[[Category: Sewell, A K]] | [[Category: Sewell, A K]] | ||
Revision as of 16:14, 10 May 2019
Porcine (Sus scrofa) Major Histocompatibility Complex, class I, with human beta2 micro globulin, presenting DFEREGYSLPorcine (Sus scrofa) Major Histocompatibility Complex, class I, with human beta2 micro globulin, presenting DFEREGYSL
Structural highlights
Disease[B2MG_HUMAN] Defects in B2M are the cause of hypercatabolic hypoproteinemia (HYCATHYP) [MIM:241600]. Affected individuals show marked reduction in serum concentrations of immunoglobulin and albumin, probably due to rapid degradation.[1] Note=Beta-2-microglobulin may adopt the fibrillar configuration of amyloid in certain pathologic states. The capacity to assemble into amyloid fibrils is concentration dependent. Persistently high beta(2)-microglobulin serum levels lead to amyloidosis in patients on long-term hemodialysis.[2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] Function[B1PJV3_PIG] Involved in the presentation of foreign antigens to the immune system.[SAAS:SAAS00291881] [B2MG_HUMAN] Component of the class I major histocompatibility complex (MHC). Involved in the presentation of peptide antigens to the immune system. Publication Abstract from PubMedThere is increasing evidence that induction of local immune responses is a key component of effective vaccines. For respiratory pathogens, for example tuberculosis and influenza, aerosol delivery is being actively explored as a method to administer vaccine antigens. Current animal models used to study respiratory pathogens suffer from anatomical disparity with humans. The pig is a natural and important host of influenza viruses and is physiologically more comparable to humans than other animal models in terms of size, respiratory tract biology and volume. It may also be an important vector in the birds to human infection cycle. A major drawback of the current pig model is the inability to analyze antigen-specific CD8+ T-cell responses, which are critical to respiratory immunity. Here we address this knowledge gap using an established in-bred pig model with a high degree of genetic identity between individuals, including the MHC (Swine Leukocyte Antigen (SLA)) locus. We developed a toolset that included long-term in vitro pig T-cell culture and cloning and identification of novel immunodominant influenza-derived T-cell epitopes. We also generated structures of the two SLA class I molecules found in these animals presenting the immunodominant epitopes. These structures allowed definition of the primary anchor points for epitopes in the SLA binding groove and established SLA binding motifs that were used to successfully predict other influenza-derived peptide sequences capable of stimulating T-cells. Peptide-SLA tetramers were constructed and used to track influenza-specific T-cells ex vivo in blood, the lungs and draining lymph nodes. Aerosol immunization with attenuated single cycle influenza viruses (S-FLU) induced large numbers of CD8+ T-cells specific for conserved NP peptides in the respiratory tract. Collectively, these data substantially increase the utility of pigs as an effective model for studying protective local cellular immunity against respiratory pathogens. Induction of influenza-specific local CD8 T-cells in the respiratory tract after aerosol delivery of vaccine antigen or virus in the Babraham inbred pig.,Tungatt K, Dolton G, Morgan SB, Attaf M, Fuller A, Whalley T, Hemmink JD, Porter E, Szomolay B, Montoya M, Hammond JA, Miles JJ, Cole DK, Townsend A, Bailey M, Rizkallah PJ, Charleston B, Tchilian E, Sewell AK PLoS Pathog. 2018 May 17;14(5):e1007017. doi: 10.1371/journal.ppat.1007017., eCollection 2018 May. PMID:29772011[15] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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