Fifteen physicochemical descriptors of side chains of the 20 natural and of 26 non‐coded amino acids are compiled and simple methods for their evaluation described. The relevance of these parameters to account for hydrophobic, steric, and electric properties of the side chains is assessed and their intercorrelation analyzed. It is shown that three principal components, one steric, one bulk, and one electric (electronic), account for 66% of the total variance in the available set. These parameters may prove to be useful for correlation studies in series of bioactive peptide analogues.
Affinity maturation of IgG antibodies in adaptive immune responses is a well-accepted mechanism to improve effector functions of IgG within 2 weeks to several months of antigen encounter. This concept has been defined mainly for IgG responses against chemically defined haptens. We have evaluated this concept in a viral system and analyzed neutralizing IgG antibody responses against vesicular stomatitis virus (a close relative of rabies virus) with a panel of monoclonal antibodies obtained early (day 6 or 12) and late (day 150) after hyperimmunization. These neutralizing IgG antibodies recognize a single major antigenic site with high affinities (Ka of 108-1010 litermol-1) and with rapid on-rates already on day 6 of a primary response and with no evidence for further antigen dose-and time-dependent overall improvement of affinity. This type of IgG response is probably representative for viruses or bacterial toxins which are crucially controlled by neutralizing antibodies.Studies with chemically defined small antigenic determinants-i.e., haptens-linked to a carrier protein have shown that during the immune response the late antibodies exhibit higher affinities (1) and faster on-rates (1-6) than early IgG antibodies. However, affinity maturation of an IgG antibody response taking more than a week may not be efficient enough against bacterial toxins or those cytopathic viruses where neutralizing antibodies are essential for protection, because too few antibodies may be generated too late (7-9).Vesicular stomatitis virus (VSV) is closely related to rabies virus and can infect many species; it may cause a paralytic disease after experimental peripheral infection in mice (10,11). Neutralizing IgG antibody responses specific for the viral glycoprotein of rabies virus or VSV are necessary for and efficient in protecting vertebrate hosts against infection (12-15). Interestingly, naive specific pathogen-free or conventionally kept mice generate T-cell-independent neutralizing IgM antibodies very early after infection, by day 3 or 4 (16, 17); the strictly T-cell-dependent (18) switch to IgG is observed by days 6-8. This represents a truly primary response, since VSVprimed mice exhibit an accelerated IgG response by days 2-4. High neutralizing titers of 10-4 to 10-5 are reached by days 9-12 after a primary infection and usually stay rather constant for >6 months.The present study attempted to assess the time-and dosedependent neutralizing antibody responses against VSV [substrain Indiana (Ind)]. These analyses revealed that neutralizing antibodies recognized only one major antigenic site on the viral glycoprotein. A panel of monoclonal neutralizing antibodies derived from various immunization protocols by varying time and antigen doses were used to measure and compare affinities, on-rates, and neutralizing activities. The means and ranges of these values were already high on day 6 and did notThe publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marke...
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