1ur7: Difference between revisions
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[[ | ==MOLECULAR REFINEMENT OF ANTI-HLA-A2 USING LIGHT CHAIN SHUFFLING: A STRUCTURAL MODEL FOR HLA ANTIBODY BINDING== | ||
<StructureSection load='1ur7' size='340' side='right'caption='[[1ur7]]' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1UR7 FirstGlance]. <br> | |||
</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=1ur7 FirstGlance], [https://www.ebi.ac.uk/pdbsum/1ur7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ur7 ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Human leukocyte antigen (HLA) A2 is one of the most immunodominant HLA antigens. Through a process of light-chain variable domain (VL) shuffling, we analyzed the VL domains' role in anti-HLA-A2/A28-binding site diversity. This was achieved by combining a VH3-30-encoded HLA-A2/A28-specific heavy-chain variable domain with 10(4) non-immune VL domains. Twelve HLA-A2/A28-specific antibodies were subsequently identified. VL gene analysis demonstrated an absence of Vlambda domains and that all have VkappaI-encoded light chains. The affinities correlated with the VkappaI gene present, with the seven highest affinity antibodies using Vkappa domains encoded by the O18 gene segment. A 300-fold difference in affinity was observed between the 12 antibodies, and homology modeling demonstrated a correlation between electrostatic surface potential of the antigen-binding site and affinity for HLA. Overlap between the T-cell receptor-binding site and that of the antibodies was indicated by inhibition of cytotoxic T-lymphocyte killing of peptide-pulsed target cells. A model of antibody binding to HLA-A2 suggested contact with both alpha helices of the HLA molecule, such that the antigen-binding site spans the peptide-binding groove. These data increase the understanding of antibody recognition of HLA and may facilitate the production of clonotypic antibodies with peptide-specific binding. | |||
Molecular studies of anti-HLA-A2 using light-chain shuffling: a structural model for HLA antibody binding.,Watkins NA, Dafforn TR, Kuijpers M, Brown C, Javid B, Lehner PJ, Navarrete C, Ouwehand WH Tissue Antigens. 2004 Apr;63(4):345-54. PMID:15009806<ref>PMID:15009806</ref> | |||
== | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | |||
<div class="pdbe-citations 1ur7" style="background-color:#fffaf0;"></div> | |||
== References == | |||
== | <references/> | ||
< | __TOC__ | ||
</StructureSection> | |||
[[Category: Theoretical Model]] | |||
[[Category: Large Structures]] | |||
[[Category: Brown, C]] | [[Category: Brown, C]] | ||
[[Category: Dafforn, T R]] | [[Category: Dafforn, T R]] | ||
Latest revision as of 09:16, 6 October 2021
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MOLECULAR REFINEMENT OF ANTI-HLA-A2 USING LIGHT CHAIN SHUFFLING: A STRUCTURAL MODEL FOR HLA ANTIBODY BINDINGMOLECULAR REFINEMENT OF ANTI-HLA-A2 USING LIGHT CHAIN SHUFFLING: A STRUCTURAL MODEL FOR HLA ANTIBODY BINDING
Structural highlights
Publication Abstract from PubMedHuman leukocyte antigen (HLA) A2 is one of the most immunodominant HLA antigens. Through a process of light-chain variable domain (VL) shuffling, we analyzed the VL domains' role in anti-HLA-A2/A28-binding site diversity. This was achieved by combining a VH3-30-encoded HLA-A2/A28-specific heavy-chain variable domain with 10(4) non-immune VL domains. Twelve HLA-A2/A28-specific antibodies were subsequently identified. VL gene analysis demonstrated an absence of Vlambda domains and that all have VkappaI-encoded light chains. The affinities correlated with the VkappaI gene present, with the seven highest affinity antibodies using Vkappa domains encoded by the O18 gene segment. A 300-fold difference in affinity was observed between the 12 antibodies, and homology modeling demonstrated a correlation between electrostatic surface potential of the antigen-binding site and affinity for HLA. Overlap between the T-cell receptor-binding site and that of the antibodies was indicated by inhibition of cytotoxic T-lymphocyte killing of peptide-pulsed target cells. A model of antibody binding to HLA-A2 suggested contact with both alpha helices of the HLA molecule, such that the antigen-binding site spans the peptide-binding groove. These data increase the understanding of antibody recognition of HLA and may facilitate the production of clonotypic antibodies with peptide-specific binding. Molecular studies of anti-HLA-A2 using light-chain shuffling: a structural model for HLA antibody binding.,Watkins NA, Dafforn TR, Kuijpers M, Brown C, Javid B, Lehner PJ, Navarrete C, Ouwehand WH Tissue Antigens. 2004 Apr;63(4):345-54. PMID:15009806[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References |
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