PMID- 14522012
OWN - NLM
STAT- MEDLINE
DCOM- 20031112
LR  - 20190827
IS  - 0161-5890 (Print)
IS  - 0161-5890 (Linking)
VI  - 40
IP  - 6
DP  - 2003 Oct
TI  - Structural analysis of IgG2A monoclonal antibodies in relation to complement 
      deposition and renal immune complex deposition.
PG  - 307-17
AB  - This study explores the structural features of murine monoclonal IgG2a 
      anti-dinitrophenyl (DNP) antibodies that were previously shown to form immune 
      complexes (IC) differing in their capacity to bind complement, their clearance 
      from the circulation and their deposition in the kidney. Interestingly, the 
      sequence of one of these antibodies has a missing stretch of 14 amino acids 
      within FR3. Molecular modeling suggests that this sequence deletion corresponds 
      to the loss of beta-pleated sheet structure for two beta-strands (designated 4-3 
      and 4-4) on the external surface of the V(H) domain. Despite this sequence and 
      conformational abnormality, the antibody retains affinity for DNP comparable to 
      other IgG2a antibodies. Data presented here identify monoclonal IgG2a antibodies 
      that form IC with varying propensity for both complement binding and renal 
      deposition and yet have similar V(H) domain sequences. In fact, in the case of 
      two IgG2a antibodies that form IC with very different renal tropisms and 
      complement binding capacity, sequence variation within V(H) was observed only at 
      three clustered residues within FR2, a single residue within FR3 and nine 
      clustered residues spanning CDR3 and FR4. Sequence and modeling analysis also 
      yielded the paradoxical finding that an antibody forming IC with a relatively 
      high capacity to serve as a target for complement binding displays a relatively 
      low number of solvent exposed acceptor residues for C4b and C3b. These data 
      underscore the complex relationship between V domain structure, complement 
      activation and renal deposition of model IC.
FAU - Gonzalez, Melva L
AU  - Gonzalez ML
AD  - Department of Microbiology and Immunology, University of Oklahoma Health Sciences 
      Center, Biomedical Sciences Building, Room 1053, P.O. Box 26901, Oklahoma City, 
      OK 73190, USA.
FAU - Frank, Mark Barton
AU  - Frank MB
FAU - Ramsland, Paul A
AU  - Ramsland PA
FAU - Hanas, Jay S
AU  - Hanas JS
FAU - Waxman, Frank J
AU  - Waxman FJ
LA  - eng
GR  - AI 07364/AI/NIAID NIH HHS/United States
GR  - AI 41586/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Mol Immunol
JT  - Molecular immunology
JID - 7905289
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antigen-Antibody Complex)
RN  - 0 (Immunoglobulin G)
RN  - 9007-36-7 (Complement System Proteins)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Antibodies, Monoclonal/*chemistry/genetics/immunology
MH  - Antibody Affinity
MH  - Antigen-Antibody Complex/*immunology/metabolism
MH  - Binding Sites
MH  - Cloning, Molecular
MH  - Complement System Proteins/*immunology/metabolism
MH  - Immunoglobulin G/*chemistry/genetics/immunology
MH  - Kidney/*immunology/metabolism
MH  - Mice
MH  - Molecular Sequence Data
EDAT- 2003/10/03 05:00
MHDA- 2003/11/13 05:00
CRDT- 2003/10/03 05:00
PHST- 2003/10/03 05:00 [pubmed]
PHST- 2003/11/13 05:00 [medline]
PHST- 2003/10/03 05:00 [entrez]
AID - S0161589003001676 [pii]
AID - 10.1016/s0161-5890(03)00167-6 [doi]
PST - ppublish
SO  - Mol Immunol. 2003 Oct;40(6):307-17. doi: 10.1016/s0161-5890(03)00167-6.