Reactivity and structure of a mouse anti-F(ab')2 IgM. Comparison of its variable region sequences with those of a structurally close polyreactive natural IgM.
IE12 is a monoclonal IgM with strong anti-F(ab')2 activity that inhibits the binding of normal mouse IgG to self antigens. In this study, we found that this IgM was also reactive with several monoclonal antibodies (mAbs), myeloma proteins and B lymphocytes from normal BALB/c mouse. The nucleotide sequences of the variable region of the heavy and light chains of IE12 were determined, and compared to those of another mAb already described in the literature. This mAb uses the same light chain and also the same VH, D and JH segments, but unlike IE12, is polyreactive. The comparison of the amino acid composition of these two mAbs and of the computer predictions for their structure and hydrophilicity indicated that the most striking difference between them was located in the third complementarity determining region (CDR3) of the heavy chain. Indeed, they used the same D segment but translated in two different reading frames, leading to different amino acid compositions. The CDR3 of IE12 contains aliphatic amino acids, while that of the polyreactive IgM does not. In addition, IE12 has two prolines, one at each at each extremity of its D segment, that could confer a certain rigidity to this region. Finally, the CDR3 of IE12 is predicted to be hydrophobic, while the one of the polyreactive IgM is predicted to be hydrophilic and more flexible, suggesting that the hydrophilicity and the flexibility of this region might be critical for polyreactivity.
Adib-Conquy
M
M
CNRS URA 359, Institut Pasteur, Paris, France.
Gilbert
M
M
Christodoulou
C
C
Avrameas
S
S
D000595:Amino Acid Sequence; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000737:chemistry*; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000276:immunology; D001483:Base Sequence; D017931:DNA Primers / Q000737:chemistry; D005803:Genes, Immunoglobulin; D007140:Immunoglobulin Fab Fragments / Q000737:chemistry / Q000276:immunology*; D007075:Immunoglobulin M / Q000737:chemistry / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013329:Structure-Activity Relationship
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D017931:DNA Primers; D007140:Immunoglobulin Fab Fragments; D007075:Immunoglobulin M