5dd1: Difference between revisions
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==Crystal structures in an anti-HIV antibody lineage from immunization of Rhesus macaques== | |||
<StructureSection load='5dd1' size='340' side='right' caption='[[5dd1]], [[Resolution|resolution]] 1.60Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5dd1]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5DD1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5DD1 FirstGlance]. <br> | |||
</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5dd0|5dd0]], [[5dd3|5dd3]], [[5dd5|5dd5]], [[5dd6|5dd6]]</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=5dd1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dd1 OCA], [http://pdbe.org/5dd1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5dd1 RCSB], [http://www.ebi.ac.uk/pdbsum/5dd1 PDBsum]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Development of an HIV vaccine is a global priority. A major roadblock to a vaccine is an inability to induce protective broadly neutralizing antibodies (bnAbs). HIV gp41 bnAbs have characteristics that predispose them to be controlled by tolerance. We used gp41 2F5 bnAb germline knock-in mice and macaques vaccinated with immunogens reactive with germline precursors to activate neutralizing antibodies. In germline knock-in mice, bnAb precursors were deleted, with remaining anergic B cells capable of being activated by germline-binding immunogens to make gp41-reactive immunoglobulin M (IgM). Immunized macaques made B cell clonal lineages targeted to the 2F5 bnAb epitope, but 2F5-like antibodies were either deleted or did not attain sufficient affinity for gp41-lipid complexes to achieve the neutralization potency of 2F5. Structural analysis of members of a vaccine-induced antibody lineage revealed that heavy chain complementarity-determining region 3 (HCDR3) hydrophobicity was important for neutralization. Thus, gp41 bnAbs are controlled by immune tolerance, requiring vaccination strategies to transiently circumvent tolerance controls. | |||
Initiation of immune tolerance-controlled HIV gp41 neutralizing B cell lineages.,Zhang R, Verkoczy L, Wiehe K, Munir Alam S, Nicely NI, Santra S, Bradley T, Pemble CW 4th, Zhang J, Gao F, Montefiori DC, Bouton-Verville H, Kelsoe G, Larimore K, Greenberg PD, Parks R, Foulger A, Peel JN, Luo K, Lu X, Trama AM, Vandergrift N, Tomaras GD, Kepler TB, Moody MA, Liao HX, Haynes BF Sci Transl Med. 2016 Apr 27;8(336):336ra62. doi: 10.1126/scitranslmed.aaf0618. PMID:27122615<ref>PMID:27122615</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 5dd1" style="background-color:#fffaf0;"></div> | ||
[[Category: Moody, M | == References == | ||
[[Category: | <references/> | ||
__TOC__ | |||
</StructureSection> | |||
[[Category: Alam, S M]] | |||
[[Category: Bouton-Verville, H]] | |||
[[Category: Bradley, T]] | |||
[[Category: Foulger, A]] | |||
[[Category: Gao, F]] | |||
[[Category: Haynes, B F]] | |||
[[Category: Kelsoe, G]] | |||
[[Category: Keple, T B]] | |||
[[Category: Liao, H X]] | |||
[[Category: Montefiori, D C]] | |||
[[Category: Moody, M A]] | |||
[[Category: Nicely, N I]] | |||
[[Category: Parks, R]] | |||
[[Category: Pemble, C]] | [[Category: Pemble, C]] | ||
[[Category: Santra, S]] | [[Category: Santra, S]] | ||
[[Category: Tomaras, G]] | |||
[[Category: Verkoczy, L]] | |||
[[Category: Wiehe, K]] | [[Category: Wiehe, K]] | ||
[[Category: Zhang, R]] | [[Category: Zhang, R]] | ||
[[Category: | [[Category: Hiv hiv-1 gp41 mper antibody]] | ||
[[Category: Immune system]] | |||
[[Category: | |||
Revision as of 19:50, 15 May 2016
Crystal structures in an anti-HIV antibody lineage from immunization of Rhesus macaquesCrystal structures in an anti-HIV antibody lineage from immunization of Rhesus macaques
Structural highlights
Publication Abstract from PubMedDevelopment of an HIV vaccine is a global priority. A major roadblock to a vaccine is an inability to induce protective broadly neutralizing antibodies (bnAbs). HIV gp41 bnAbs have characteristics that predispose them to be controlled by tolerance. We used gp41 2F5 bnAb germline knock-in mice and macaques vaccinated with immunogens reactive with germline precursors to activate neutralizing antibodies. In germline knock-in mice, bnAb precursors were deleted, with remaining anergic B cells capable of being activated by germline-binding immunogens to make gp41-reactive immunoglobulin M (IgM). Immunized macaques made B cell clonal lineages targeted to the 2F5 bnAb epitope, but 2F5-like antibodies were either deleted or did not attain sufficient affinity for gp41-lipid complexes to achieve the neutralization potency of 2F5. Structural analysis of members of a vaccine-induced antibody lineage revealed that heavy chain complementarity-determining region 3 (HCDR3) hydrophobicity was important for neutralization. Thus, gp41 bnAbs are controlled by immune tolerance, requiring vaccination strategies to transiently circumvent tolerance controls. Initiation of immune tolerance-controlled HIV gp41 neutralizing B cell lineages.,Zhang R, Verkoczy L, Wiehe K, Munir Alam S, Nicely NI, Santra S, Bradley T, Pemble CW 4th, Zhang J, Gao F, Montefiori DC, Bouton-Verville H, Kelsoe G, Larimore K, Greenberg PD, Parks R, Foulger A, Peel JN, Luo K, Lu X, Trama AM, Vandergrift N, Tomaras GD, Kepler TB, Moody MA, Liao HX, Haynes BF Sci Transl Med. 2016 Apr 27;8(336):336ra62. doi: 10.1126/scitranslmed.aaf0618. PMID:27122615[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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