Immunoglobulin CDRs

Comparison of Vy sequences shows hypervariable regions analogous to immunoglobulin CDR s. 

Monoclonal antibody therapy (MAT) makes use of all the major features of the immune response. It involves vaccination/ immunization, albeit in experimental animals, to induce the desired specific immune response. It exploits the high specificity, selectivity, and affinity of the antibody CDR toward the target antigen to be recognized, highlighted, inactivated, or eliminated, using the characteristics of the Fc portion of an immunoglobulin to facilitate the means for such inactivation or elimination and for selection of appropriate effector mechanisms. Finally, MAT represents a modern form of serotherapy, in which parenteral administration of whole serum or Ig preparations has been replaced by recombinant antibody molecules of a defined specificity. 

Protein blocks are applied to the tissues prior to application of the primary antibody to reduce nonspecific staining. Nonspecific staining is non-CDR-mediated staining. Protein blocks often contain serum, which contain immunoglobulins that bind to the Fc receptors in the tissues, blocking Fc attachment to those tissue receptors. Other proteins such as casein or BSA may be added to block nonspecific protein-protein interactions. 

Figure 22.25. Schematic illustration of an immunoglobulin IgG. The complex consists of two heavy (H) chains and two light (L) chains. Somatic hypermutation that greatly contributes to antibody diversity occurs in the variable (V) regions of both the heavy and the light chins, especially the complementarity-determining regions (CDR).

A few aspects of antibody binding merit specific attention, inasmuch as they relate directly to the structure of immunoglobulins. The binding site on the antibody has been found to incorporate some or all of the CDRs in the variable domains of the antibody. Small molecules are likely to make contact with fewer (]DRs, with perhaps 15 residues of the antibody participating in the binding interaction. Macromolecules often make more extensive contact, sometimes interacting with all six CDRs and 20 or more... 

Abbreviations used in table MC - Monte Carlo aa - amino acid vdW - van der Waals potential Ig - immunoglobulin or antibody CDR - complementarity-determining regions in antibodies RMS -root-mean-square deviation r-dependent dielectric - distance-dependent dielectric constant e - dielectric constant MD - molecular dynamics simulation self-loops - prediction of loops performed by removing loops from template structure and predicting their conformation with template sequence bbdep - backbone-dependent rotamer library SCMF - self-consistent mean field PDB - Protein Data Bank Jones-Thirup distances - interatomic distances of 3 Ca atoms on either side of loop to be modeled. 

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