Antibody libraries

Janda, K. D., 1997. Chemical selection for catalysis in combinatorial antibody libraries. Science 275 945. 

Two types of antibody libraries can be constructed, immune or non-immune. Immune libraries are constructed by immunizing the animal of interest with an antigen(s). In the case of humans, the source can be volunteers with the disease or condition under study (Persson et al., 1991). Human antibodies have also been obtained from severe combined immunodeficiency mice populated with human peripheral blood... 

Rader, C., and Barbas, C. F., Ill (1997). Phage display of combinatorial antibody libraries. Curr. Opin. Biotechnol. 8, 503-508. 

Sblattero, D., and Bradbury, A. (2000). Exploiting recombination in single bacteria to make large phage antibody libraries. Nat. Biotechnol. 18, 75-80. 

Probes can be antibodies, other binding proteins constructed from protein fusions, or even oligonucleotide aptamers. While completion of the Human Genome Project has enabled access to content for nuclide acid arrays, the content for protein arrays is largely based upon available antibody libraries. Thus, the commercialization of protein microarrays remains largely dependent upon both commercial and institutional providers of protein content. These providers must also permit access to the data-based protein annotations. These are necessary in order for the protein array to be useful as a bioinformatics tool. 

The protein microarray represents an emerging technology. While we have described its potential utility, several key problems remain to be overcome before this tool is fully adopted by the research and biopharmaceutical commxmities. The most likely first embodiment will be an antibody "protein-detecting" microarray. This is understandable based upon the availability and suitability of antibody libraries originally developed for ELISA. We have discussed many demonstrahons of antibody arrays in this chapter but commercial introductions (Pierce, Beckman Coulter) have been limited. 

Hoet, R.M.A., Raats, J.M.H., de Wildt, R., et al. (1998). Human monoclonal autoantibody fragments from combinatorial antibody libraries directed to the UlsnRNP associated U1C protein) epitope mapping, immunolocalization and V-gene usage. Mol. Immunol., 35, 1045-1055. 

Soderlind, E., Strandberg, L., Jirholt, P., et al. (2000). Recombining germline-derived CDR sequences for creating diverse single-framework antibody libraries. Nat. Biotechnol., 18, 852-856. 

Barbas, C F, III, Bain, J. D, Hoekstra, D M and Lemer, R. (1992) Semisynthetic combinatorial antibody libraries- A chemical solution to the diversity problem Proc. Natl. Acad Sci USA 89,4457-4461... 

Barbas, C. F., Kang, A. S., Lemer, R. A, and Benkovic, S. J. (1991) Assembly of combinatorial antibody libraries on phage surfaces (Phabs)- the gene III site Proc Natl. Acad Sci USA 88, 7978-7982. 

The dimension of an antibody library, typically defined as the number of clones bearing a suitable selectable marker (antibiotic resistance) and, containing the full-size antibody gene (detectable by PCR screening 32), does not necessarily correspond to the functional dimension of a library, which requires that the clones express properly folded antibodies. An approximation for the determination of the functional dimension of a library consists of determining what percentage of clones expresses antibodies, for example, using immunoblot techniques. 

De Kruif, J., Terstappen, L, Boel, E, and Logtenberg, T (1995) Rapid selection of cell subpopulation-specific human monoclonal antibodies from a synthetic phage antibody library Proc Natl Acad Sci. USA 92, 3938—3942... 

Hoogenboom HR. 2005. Selecting and screening recombinant antibody libraries. Nat Biotech. 23 1117-1125. 

Assembly of combinatorial antibody libraries on phages surfaces the gene III site. Proc. Natl. Acad. Sci. USA 88,7987-7982. 

Knappik, A., Ge, L., Honegger, A., Pack, P., Fischer, M., Wellnhofer, G., et al. (2000) Fully synthetic human combinatorial antibody libraries (HuCAL) based on modular consensus framework and CDRs randomized with trinucleotides. J. Mol. Biol. 296,57-86. 

Sheets, M. D., Amersdorfer, P., Finnem, R., Sargent, P., Lindqvist, E., Schier, R., et al. (1998) Efficient construction of a large nonimmune phage antibody library the production of high-affinity human single-chain antibodies to protein antigens. Proc. Natl. Acad. Sci. USA 95, 6157-6162. 

Den, W., Sompuram, S. R., Sarantopoulos, S., and Sharon, J. (1999) A bidirectional phage display vector for the selection and mass transfer of polyclonal antibody libraries. J. Immunol. Meth. 222, 45-57. 

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