Do antibodies recognize amino acid side chains of protein antigens independently of the carbon backbone?

Abstract

An integral component within Jerne's idiotype network theory (1) is the internal image antibody (Ab) 1 that bears determinants within the variable (V) region resembling external antigens . Internal images mimicking viruses, bacteria, protozoa, and natural ligands have been described (2-5) and have generated interest in their use as potential vaccines and probes for cellular receptors (6). The structural basis for internal image expression, however, remains largely unknown. Two recent studies using the synthetic (Glub°Ala 3°Tyrt°) terpolymer (7) and the reovirus hemagglutinin (8) have identified determinants in Ab internal image V regions that appear to match linear or continuous sequences within each respective antigen. Further insight into the molecular nature of internal images and the rules that govern antigen recognition will be crucial for the rational design of internal image vaccines and an understanding of idiotypic interactions .To investigate internal image expression in a well-defined protein system, we have used the al allotype of rabbit Ig as a model antigen (9-11) and have isolated two mouse mAbs that bear al-like determinants within their antigen-binding sites (12). We have now obtained the V region amino acid sequences of these internal images and have found that both mAbs contain a unique sequence of identity with rabbit Ig but in a novel configuration. The data, coupled with results from synthetic peptide inhibition experiments, indicate that an amino acid sequence oriented in reverse direction on an internal image molecule can effectively mimic the nominal antigen .

Quaternary structure-dependent idiotope and antigen binding of a monoclonal antibody specific for conformational epitope on type II collagen

“…A similar mode of antigen mimicry by anti-idiotypic Abs, i.e. a portion of Ab V region resembling an epitope of an external antigen, has been also noted for different antigen/Ab systems [25][26][27]. Differing from the earlier observations, we found no homology between mAb2 and CII at the primary amino acid sequence level ( fig.…”

Generation of biologically active linear and cyclic peptides has revealed a unique fine specificity of rituximab and its possible cross-reactivity with acid sphingomyelinase-like phosphodiesterase 3b precursor

“…Finally, the possibility that antibodies can recognize amino acid side chains independently of the carbon-backbone direction, 34,35 as indicated by the reactivity of rituximab with both pASMLPD and rev-pASMLPD, suggested that binding of rituximab to this enzyme is possible. Whether this interaction contributes to the rapid and transient increase in acid sphingomyelinase activity in raft microdomain 13 remains to be determined.…”

Human CD4 internal antigen anti-idiotypic monoclonal antibody. Immunochemical and sequence analysis

“…In this approach, mAb2-VH and -VL have been mostly used in direct orientation, although in the rabbit a1 allotype system, similarity between the Ag and mAb2 has also been demonstrated by using its VH in reverse orientation [33]. The goal of this study was to define the molecular basis of structural mimicry of CD4 by 16D7, in order to define whether or not 16D7 VH and/or VL-derived peptides with similarity to CD4 can be obtained.…”

“…Alignment of CD4 with 16D7-VH produced five and three peptides using VH in direct and reverse [33] orientation, respectively. None was similar to 16D7-H CDR3.…”