1ur7

Theoretical Model: The protein structure described on this page was determined theoretically, and hence should be interpreted with caution.

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 For a guided tour on the structure components use FirstGlance. Resources: FirstGlance, PDBsum, ProSAT 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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