Antibodies framework regions

S-Fl Jung, I Pastan, B Lee. Design of interchain disulfide bonds m the framework region of the Fv fragment of the monoclonal antibody B3. Pi otems 19 35-47, 1994. 

The residues not in the framework region form the loops between the p strands. These loops may vary in length and sequence among immunoglobulin chains of different classes but are constant within each class the sequence of the loops is invariant. The functions of these loops are not known, but they are probably involved in the effector functions of antibodies. When an antibody-antigen complex has been formed, signals are... 

Further progress was achieved by the humanization of murine antibodies. In humanized mAbs, the murine fraction of 5-10% consists only of the murine CDRs and, if necessary, some exclusive parts of the framework region. The human immune system can also produce antibodies against these humanized antibodies, so-called human anti-human antibodies (HAHAs). 

The REM, NK and p-spin models all are attempts to capture the important statistical properties of true molecular landscapes in a simple model. Because they contain no biophysical information, they are limited in how well they can achieve this. The block model is an important step in removing some of the simplifications in these models, as it allows for nonstationary properties that can be matched to different regions of molecules. Ideally, landscape models can be based on experimental data. Unfortunately, despite the tremendous interest in molecular optimization, there is still relatively little data that can be used this way. As more data are collected on the effects of substitutions in protein structural and loop regions, antibody CDRs and framework regions, etc., a block or other type of model can be developed that uses appropriate fitness functions for each block. Combined efforts by theoreticians and experimentalists may also help devise experiments that measure key true affinity landscape properties without excessive laboratory effort. 

Azriel-Rosenfeld, R. Valensi, M. Benhar, I., A human synthetic combinatorial library of arrayable single-chain antibodies based on shuffling in vivo formed cdrs into general framework regions,./. Mol. Biol. 2004, 335, 177-192... 

Trastuzumab is a rDNA-derived humanized MAb, an igGI kappa that contains human framework regions with the compiementarity-determining regions of a murine antibody (4D5) that binds to HER2. 

---