The principal aim of this project is to test the hypothesis of general multispecificity for the combining regions of antibodies and other kinds of receptors. Receptor sites, according to theory developed earlier in this project, should be capable of interacting with virtually any substance in a manner that will lower the standard free energy of the system and thus exhibit an equilibrium association constant greater than 1. Most associations will be weaker than ones commonly measured, but occasional substances may bind to a receptor with affinities high enough to affect biological function. Their structure may not necessarily resemble those of the recognized effector, substrate or antigen. The above hypothesis is being tested in the following way: Radiolabeled, monoclonal antibodies or solubilized receptors are passed through small, affinity chromatography columns. Accurate measurements are made of the retention (retardation) caused by a matrix-bound reference ligand in the presence and absence of many, diverse, suitably large compounds. The resulting retention values are employed directly in calculating association constants for these compounds and the receptor site. The distribution of affinities provides a description of the receptor's multispecific character. The technique of quantitative affinity chromatography, developed in this study, provides a general means for estimating very low to moderately strong association constants. Knowledge of multispecific interactions will be employed in re-evaluating general concepts of specificity in biological recognition. Special attention will be given to applying these findings to models of immune systems and control networks.
| Eller, Nancy; Golding, Hana; Inoue, Satoshi et al. (2004) Systemic and mucosal immunity in rhesus macaques immunized with HIV-1 peptide and gp120 conjugated to Brucella abortus. J Med Primatol 33:167-74 |
| Golding, Basil; Eller, Nancy; Levy, Lily et al. (2002) Mucosal immunity in mice immunized with HIV-1 peptide conjugated to Brucella abortus. Vaccine 20:1445-50 |
| Shafer, D E; Inman, J K; Lees, A (2000) Reaction of Tris(2-carboxyethyl)phosphine (TCEP) with maleimide and alpha-haloacyl groups: anomalous elution of TCEP by gel filtration. Anal Biochem 282:161-4 |
| Metzger, H; Chen, H; Goldstein, B et al. (1999) A quantitative approach to signal transduction. Immunol Lett 68:53-7 |
| Wofsy, C; Vonakis, B M; Metzger, H et al. (1999) One lyn molecule is sufficient to initiate phosphorylation of aggregated high-affinity IgE receptors. Proc Natl Acad Sci U S A 96:8615-20 |
