Immune Response to Chemically Modified Flagellin

Abstract

In the preceding paper (1) some chemical, antigenic, and biological properties of a series of acetoacetylated derivatives of Salmonella adelaide flagellin were described. Several chemical and antigenic tests revealed that as flagellin was acetoacetylated to increasing extents there was a steady decline in the affinity of the molecule for anti-flagellin antibodies. This loss in antigenic activity appeared to be accompanied on the one hand by a reduced capacity to initiate antibody formation but on the other hand b y an enhanced ability to induce antibody tolerance. In this paper the antibody tolerance induced by these acetoacetylated flagellins is studied in more detail. Furthermore, the ability of these acetoacetyl derivatives to induce delayed-type hypersensitivity is reported. F r o m these studies it was found that suppression of antibody formation in adult rats was accompanied by enhanced cell-mediated immunity. In fact, it appears that in adult animals antibody formation and cell-mediated immunity m a y well be opposing immunological processes. By contrast, tolerance induced in neonatal rats by acetoacetyl flagellin existed at the level of both humoral and cell-mediated immunity. Some preliminary aspects of this work have been reported elsewhere. 1 Materials and MethodsAnimals.--Randomly bred Wistar rats of either sex were used. Animals were either obtained directly from the Walter and Eliza Hall Institute of Medical Research, Parkville, Australia, or bred in Canberra from Wistar breeders supplied by the Walter and Eliza Hall Institute. Both adult (6-10 wk of age) and neonatal rats were used.Antigens.--Flagellin and polymerized flagellin from S. adelaide (strain SW 1338; H antigen--fg) and flagellin from S. typhimurium (strain SL 871; H antigen--l, 2) were prepared as described previously (2). A cyanogen bromide (CNBr) digest of S. adelaide flagellin was prepared and fractionated into fragment A and a mixture of fragments B, C, and D as de-1 Parish, C. R. 1971. Suppression of antibody formation and concomitant enhancement of cell-mediated immunity by acetoacetylated derivatives of Salmonella flage]lin.

Immunogenicity of tumour cells modified with various chemicals

“…The number of modifying groups per cell differed from saturation by a factor of 2 at most, thus following the findings obtained with protein antigens (Parish, 1971;Staab and Anderer, 1976). Considering the membrane structure and the type of chemical reagents used, one has to assume that the modifying groups had reacted with sites not only on the cell surface but also inside the cell.…”

“…One of the factors influencing the immunogenicity of an antigen has been shown to be the number of modifying groups per antigen molecule (Parish, 1971;Staab and Anderer, 1976). The immunogenic capacity to induce specific cellular immune responses increased with increasing numbers of modifying groups, but optimal effects were achieved before all the reactive sites of the antigen had reacted (Parish, 1971).…”

“…The immunogenic capacity to induce specific cellular immune responses increased with increasing numbers of modifying groups, but optimal effects were achieved before all the reactive sites of the antigen had reacted (Parish, 1971).…”

“…In our study we selected modifying groups which were aliphatic, of small size and, when conjugated with proteins, were known to induce cellular immunity against protein antigens without inducing humoral antibodies against the modifying groups (Parish, 1971;Coon and Hunter, 1972;Thompson, Harries and Benjamini, 1972;Staab and Anderer, 1976;Benacerraf and Gell, 1959). The number of modifying groups per cell differed from saturation by a factor of 2 at most, thus following the findings obtained with protein antigens (Parish, 1971;Staab and Anderer, 1976).…”

“…INVESTIGATIONS directed towards determining the influence of chemical modification on the immunogenicity of antigens have been reported by several groups (Parish, 1971;Coon and Hunter, 1972;Thompson, Harries and Benjamini, 1972;Staab and Anderer, 1976). In several cases stimulation predominantly of the cellular immune response could be achieved.…”