Monoclonal antibodies specificity

The first mouse monoclonal antibody specific for human CD3 was produced in 1979 and named orthoclone OKT3. Aside from its use in the laboratory, OKT3 became the first anti-CD3 antibody to be utilized in transplantation medicine, but its wider application was hampered by its immunogenic and mitogenic properties (reviewed in [6]). Consequently, humanized and engineered anti-CD3 antibodies were developed to circumvent these limitations (Table 1). Since T cells and the TCR are involved in many immunological diseases, it is not surprising that the application of CD3 antibodies is not restricted to the field of transplantation. For example, CD3 antibodies are tested in clinical studies of diseases such as autoimmune diabetes (type 1 diabetes), immune-mediated inflammatory arthritis and inflammatory bowel disease [7]. 

When an antigen is injected into an animal, the resulting antibodies are polyclonal, being synthesized by a mixture of B cells. Polyclonal antibodies are directed against a number of different sites (epitopes or determinants) on the antigen and thus are not monospecific. However, by means of a method developed by Kohler and Milstein, large amounts of a single monoclonal antibody specific for one epitope can be obtained. 

Enzyme-Mediated Substrate Immunolocalization ofPoIygalacturonic Acid Within Barley Epidermal Cell Walls Utilizing Endopolygalacturonase of Cochliobolus sativus and a Monoclonal Antibody Specific for the Enzyme... 

Palinski, W., Yla-Herttuala, S., Rosenfeld, M.E., Butler, S.W., Socher, S.A., Parthasarathy, S., Curtiss, L.K. and Witztum, J.L. (1990). Antisera and monoclonal antibodies specific for epitopes generated during oxidative modification of low density lipoproteins. Arteriosclerosis 10, 325-335. 

EDTA Ethylenediamine tetraacetic acid ako known as etidronic acid EE Eosinophilic eosinophils EEG Electroencephalogram EET Epoxyeicosatrienoic acid EFA Essential fatty acid EFS Electrical field stimulation EGl Monoclonal antibody specific for the cleaved form of eosinophil cationic peptide... 

Adalimumab is a recombinant human IgGl monoclonal antibody specific for human TNF.27 Adalimumab binds to soluble and bound TNF-a. Patients may experience symptomatic relief in as early as 1 week. Adalimumab can be administered in combination with methotrexate or other DMARDs.2... 

Figure 7.1. Protein expression mapping using an antibody array. The antibody array consists of monoclonal antibodies specific for a set of proteins in the organism of interest gridded onto a filter. To determine if a protein is expressed under the conditions being tested, a crude lysate is obtained and the proteins within the lysate are labeled with a fluorescent tag. The lysate is applied to the filter and the proteins are allowed to bind to the relevant antibody. Bound proteins are visualized via the fluorescent tag.

Woodward, M.P., Young, W.W., and Bloodgood, R.A. (1985) Detection of monoclonal antibodies specific for carbohydrate epitopes using periodate oxidation./. Immunol. Meth. 78, 143-153. 

Most T-helper cells express a membrane protein termed CD4 on their surface. Most T-cytotoxic and T-suppressor cells produce a different cell surface protein, termed CD8. Monoclonal antibodies specifically recognizing CD4 or CD8 proteins can thus be used to differentiate between some T cell types. 

King, D.P. et al., The use of monoclonal antibodies specific for seal immunoglobulins in an enzyme-linked immunosorbent assay to detect canine distemper virus-specific immunoglobulin in seal plasma samples, J. Immuno. Methods, 160, 163, 1993. 

Clinically, monoclonal antibodies are also proposed as drug delivery vehicles in certain tumors where specific tumor-associated antigens are expressed. In this context, investigators have found that by conjugating toxins such as the A chain polypeptide of the plant protein ricin or the bacterial toxin from Corynebacterium diphtheriae to monoclonal antibodies specific for certain tumor type, as few as one or two molecules of antibody-toxin conjugate can destroy a tumor cell in vitro. Some success has also been obtained in clinical trials with monoclonal antibody-toxin conjugates. 

The membrane fusion activity is probably a function of the El protein, since the hemolytic activity of Sindbis virus can be inhibited by monoclonal antibodies specific for El (Chanas et al., 1982). Moreover, studies using cDNA molecules coding for the spike proteins have shown that if the spike protein is expressed at the cell surface, fusion between cells is induced at low pH. However, when the p62 protein is expressed alone, no fusion occurs (Kondor-Koch et al., 1983). 

Libraries can also be made from naturally occurring peptides (e.g. melanocortin [30] and somatostatin [31]) and their variants, or be derived from protein-fragments. The former have been employed mainly for the identification of peptide variants with unproved characteristics, and the latter for the identification of antigenic determinants present on targets, for example by selecting for binders to monoclonal antibodies specific for an antigen-fragment peptide library. 

Even greater flexibility was achieved by genetic fusion of streptavidin with protein A [153,154]. Protein A specifically binds the Fc domain of IgG immunoglobulins of almost all mammals without inhibiting the antigen binding activity of the antibody. The streptavidin-protein A fusion construct was used for the assembly of complexes of biotinylated P-galactosidase and different monoclonal antibodies specific for tumour cell receptors. As a result these complexes were efficiently delivered into several cancer cell lines [154]. 

Nielsen et al. used this method to separate antigen-antibody complexes of recombinant hGH with monoclonal antibody specific to hGH (12). The complexes were well resolved from the free antibody and antigen in solution. The strong binding affinity of the antibody for hGH results in strong, stable antibody-antigen complexes that form very rapidly in solution two complexes (IgG-hGH, IgG-(hGH)2) have been observed. 

Nl. Nagata, S., Tsutsumi, T., Yoshida, R, and Ueno, Y, A new type sandwich immunoassay for microcystin Production of monoclonal antibodies specific to the immune complex formed by microcystin and an anti-microcystin monoclonal antibody. Natural Toxins 1, 49-55 (1999). 

Griffin, H.M., and W.H. Onwehand, A human monoclonal antibody specific for the leucine-33 (PlAl, HPA-laj form of platelet glycoprotein Ilia from a V gene phage display library. Blood, 1995. 86(12) 4430-6. 

Capromab pendetide is a murine monoclonal antibody specific for prostate specific membrane antigen. It is coupled to isotopic indium (111In) and is used in immunoscintigraphy for patients with biopsy-confirmed prostate cancer and post-prostatectomy in patients with rising prostate specific antibody level to determine extent of disease. 

Class Immunosuppressive chimeric monoclonal antibody, specifically binds to and blocks the interleukin-2 receptor alpha chain on the surface of activated T- lymphocytes... 

A major application of monoclonal antibodies is in clinical assays for drugs, bacterial and viral products, tumor antigens, hormones, and other circulating proteins. Their use in conjunction with immunoassays (Box 31-C) has provided increased specificity and sensitivity. Another major application is to observe binding of antibodies to specific proteins by electron microscopy. The location of specific receptor proteins can be established - as can the locations of ribosomal proteins and many other cellular components (Fig. 29-1). Monoclonal antibodies to acetylcholine receptors have been shown to induce symptoms of myasthenia gravis (Box 31-D), supporting the autoimmune origin of that disease. 1 Monoclonal antibodies specific for such a small hapten as mercuric ion have been isolated.k... 

Many attempts have been made to link monoclonal antibodies specific for antigenic determinants on cancer cells to protein toxins such as ricin (Box 29-A). It is hoped that this may provide an effective way of carrying toxins into cancer cells/ 1 r Therapeutic human monoclonal antibodies are already in use as antirejection drugs for kidney transplantation, for treatment of rheumatoid arthritis, Crohn disease, and for some types of cancer/... 

Evan, G. I, Lewis, G. K, Ramsay, G, and Bishop, J M (1985) Isolation of monoclonal antibodies specific for the human c-myc protooncogene product. Mol Cell Biol 5,3610-3616... 

Harn, D.A., Cu, W., Oligino, L.D., Mitsuyama, M., Gebremichael, A. and Richter, D. (1992) A protective monoclonal antibody specifically recognizes and alters the catalytic activity of schistosome triose-phosphate isomerase. The Journal of Immunology 148, 562-567. 

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