PMID- 10524770
OWN - NLM
STAT- MEDLINE
DCOM- 19991102
LR  - 20200225
IS  - 0277-8033 (Print)
IS  - 0277-8033 (Linking)
VI  - 18
IP  - 5
DP  - 1999 Jul
TI  - Antibody immunodiversity: a study on the marked specificity difference between
      two anti-yeast iso-1 cytochrome c monoclonal antibodies whose epitopes are
      closely related.
PG  - 523-32
AB  - Anti-yeast iso-1 cytochrome c (cyt. c) monoclonal antibodies 2-96-12 and 4-74-6
      have closely related epitopes (antigenic determinants). However, while the
      specificity of 4-74-6 is stringent, 2-96-12 cross-reacts with many evolutionarily
      related cytochromes c. Such a marked difference in specificity of antibodies with
      overlapping epitopes may represent unique antibody immunodiversity. Thus, we
      constructed Fv fragment models consisting of the variable domains of the heavy
      and light chains of 2-96-12 and 4-74-6 and that of another anti-iso-1 cyt. c as a
      control to gain insight into the origin of this difference in specificity. Our
      models show that 4-74-6 and 2-96-12 contain five and two aromatic side chains,
      respectively, in or near the central area of the antigen-combining site. The side
      chains of Arg95H (heavy chain) in 2-96-12 and Arg91L (light chain) in 4-74-6
      project toward the central area of the combining site in our model. Antigen
      docking to our Fv models, combined with previous immunological studies, suggests 
      that iso-1 cyt. c Asp60 may interact with Arg95H in 2-96-12 and Arg91L in 4-74-6 
      and that both epitopes of 2-96-12 and 4-74-7 may include iso-1 cyt. c Leu58,
      Asp60, Asn62, and Asn63. The effect of the Arg95H to Lys mutation on the antigen 
      binding is also in accord with our model. The difference in specificity may be
      partly explained by a greater degree of conformational flexibility in and around 
      the central area of the combining site in 2-96-12 compared to 4-74-6 due to
      differences in aromatic side chain packing.
FAU - Rizzo, P
AU  - Rizzo P
AD  - Laboratory of Chemical Biology, National Institute of Diabetes and Digestive and 
      Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
FAU - Tinello, C
AU  - Tinello C
FAU - Pearlstein, R A
AU  - Pearlstein RA
FAU - Taniuchi, H
AU  - Taniuchi H
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Protein Chem
JT  - Journal of protein chemistry
JID - 8217321
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (CYC1 protein, S cerevisiae)
RN  - 0 (Cytochrome c Group)
RN  - 0 (Epitopes)
RN  - 0 (Saccharomyces cerevisiae Proteins)
RN  - 9007-43-6 (Cytochromes c)
SB  - IM
MH  - Amino Acid Sequence
MH  - Amino Acid Substitution
MH  - Antibodies, Monoclonal/*chemistry/genetics
MH  - *Antibody Specificity
MH  - Cytochrome c Group/*immunology
MH  - *Cytochromes c
MH  - Epitopes/*chemistry/genetics
MH  - Models, Molecular
MH  - Molecular Sequence Data
MH  - Saccharomyces cerevisiae/*enzymology
MH  - *Saccharomyces cerevisiae Proteins
MH  - Sequence Homology, Amino Acid
EDAT- 1999/10/19 00:00
MHDA- 1999/10/19 00:01
CRDT- 1999/10/19 00:00
PHST- 1999/10/19 00:00 [pubmed]
PHST- 1999/10/19 00:01 [medline]
PHST- 1999/10/19 00:00 [entrez]
AID - 10.1023/a:1020695031952 [doi]
PST - ppublish
SO  - J Protein Chem. 1999 Jul;18(5):523-32. doi: 10.1023/a:1020695031952.