Do antibodies recognize amino acid side chains of protein antigens independently of the carbon backbone?
In an effort to understand the structural basis for antigen mimicry by internal image antibodies, we determined the variable (V) region sequences of two mouse mAbs that mimic the rabbit Ig a1 allotype. The results showed that while the mAb light chains did not contain any allotype-related residues, both heavy chain V regions contained within complementarity-determining region 2 an unusual sequence homologous to the nominal antigen but in opposite orientation with respect to the carbon backbone. The ability of the internal image reversed sequence to express an a1-like determinant was tested directly by producing synthetic peptides that corresponded to the presumed antigenic regions of rabbit Ig and the mAb internal images, respectively. Although the two peptides presented the homologous residues in opposite orientations, they both completely inhibited at similar concentrations the binding of rabbit Ig to anti-a1 antibody. Conservative substitutions in the peptide sequence identified a paired Thr and Glu as being critical for expression of the a1 epitope. These findings indicate that antibodies can recognize the molecular environments created by amino acid side chains independently from the orientation of the protein carbon backbone.
Van Cleave
V H
VH
Department of Immunology, St. Jude Children's Research Hospital, Memphis, Tennessee 38101.
Naeve
C W
CW
Metzger
D W
DW
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001666:Binding Sites, Antibody; D000939:Epitopes; D007126:Immunoglobulin Allotypes / Q000276:immunology; D007143:Immunoglobulin Heavy Chains / Q000276:immunology; D007147:Immunoglobulin Light Chains / Q000276:immunology; D007135:Immunoglobulin Variable Region / Q000276:immunology; D008969:Molecular Sequence Data; D011487:Protein Conformation; D011506:Proteins / Q000276:immunology*; D011817:Rabbits; D013329:Structure-Activity Relationship
D000939:Epitopes; D007126:Immunoglobulin Allotypes; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D007135:Immunoglobulin Variable Region; D011506:Proteins