2AAB

Structural basis of antigen mimicry in a clinically relevant melanoma antigen system

Summary for 2AAB

• Entry DOI: 10.2210/pdb2aab/pdb
• Descriptor: anti-idiotypic monoclonal antibody (light chain), anti-idiotypic monoclonal antibody (heavy chain) (3 entities in total)
• Functional Keywords: anti-idiotypic antibody, molecular mimicry, melanoma, immunotherapy, immune system
• Biological source: Mus musculus (house mouse); More
• Total number of polymer chains: 2
• Total formula weight: 50227.13

Authors

Chang, C.-C.,Hernandez-Guzman, F.G.,Luo, W.,Wang, X.,Ferrone, S.,Ghosh, D. (deposition date: 2005-07-13, release date: 2005-10-25, Last modification date: 2024-11-20)

Primary citation

Chang, C.-C.,Hernandez-Guzman, F.G.,Luo, W.,Wang, X.,Ferrone, S.,Ghosh, D.
Structural basis of antigen mimicry in a clinically relevant melanoma antigen system.
J.Biol.Chem., 280:41546-41552, 2005

PubMed Abstract: Although mimics of human tumor antigens are effective immunogens to overcome host unresponsiveness to the nominal antigen, the structural basis of this mimicry remains poorly defined. Therefore, in this study we have characterized the structural basis of the human high molecular weight-melanoma-associated antigen (HMW-MAA) mimicry by the mouse anti-idiotypic (anti-id) monoclonal antibody (mAb) MK2-23. Using x-ray crystallography, we have characterized the three-dimensional structure of the anti-id mAb MK2-23 Fab' and shown that its heavy chain complementarity-determining region (CDR3) (H3) and its light chain CDR1 (L1) are closely associated. These moieties are the source of HMW-MAA mimicry, since they display partial amino acid sequence homology along with a similar structural fold with the HMW-MAA core protein. Furthermore, a 15-residue peptide comprising the H3 loop of anti-id mAb MK2-23 demonstrates HMW-MAA-like in vitro and in vivo reactivity. This peptide in conjunction with the structural data will facilitate the characterization of the effect of the degree of antigen mimicry on the induction of a self-antigen-specific immune response by a mimic.

PubMed: 16227204
DOI: 10.1074/jbc.M507562200

Experimental method

X-RAY DIFFRACTION (2.5 Å)