Dominance of Immunoglobulin G2c in the Antiphosphorylcholine Response of Rats Infected withTrichinella spiralis

Abstract

The antibody response to the L1 stage of Trichinella spiralis has been described as biphasic. Worms resident in the intestine during the first week of infection stimulate an antibody response against a subset of larval proteins. L1 larvae in the muscle at the end stage of infection stimulate a second antibody response against tyvelose-bearing glycoproteins. Antityvelose antibodies protect rats against challenge infection with larvae. The aim of this study was to characterize the rat B-cell response against larval antigens during the intestinal phase of T. spiralis infection and to test the antiparasitic effects of such antibodies. Strain PVG rats were infected orally with 500 larvae. Antibodies specific for phosphorylcholine-bearing proteins of L1 larvae first appeared in serum 9 days postinfection. Absorption experiments showed that the majority of antilarval antibodies produced in rats 16 days after infection withT. spiralis were specific for phosphorylcholine-bearing proteins. A fraction of these antibodies bound to free phosphorylcholine. Immunoglobulin G2c (IgG2c) producing cells in the mesenteric lymph node dominated this early antibody response. IgG2c is associated with T-independent immune responses in the rat; however, a comparison of athymic rats with euthymic controls suggested that only a small fraction of the phosphorylcholine-related antibody response against T. spiralis was T independent. Phosphorylcholine is a common epitope in antigens of bacteria and nematode parasites and has been shown to be a target of protective immunity in certain bacteria. A monoclonal IgG2c antibody was prepared from infected rats and shown to be specific for phosphorylcholine. Monoclonal phosphorylcholine-specific IgG2c failed to protect rats against intestinal infection with T. spiralis. Therefore, our findings do not support a role for phosphorylcholine-bearing antigens in immune defense against T. spiralis; however, the potency of the immune response induced suggests an immunomodulatory role for the lymphocytes involved.

Influence of Carrier Protein Conjugation Site and Terminal Modification of a GnRH‐I Peptide Sequence in the Development of a Highly Specific Anti‐fertility Vaccine. Part I

“…For HWSYGLRPGC‐TT, the main subclasses were IgG2a and IgG1, whereas with TT‐CHWSYGLRPG‐NH 2 , in addition to these major subclasses, IgG2c was also observed. It is believed that IgG1 and IgG2a production in the rat is an indicator of both humoral and cellular immunization; 27 while IgG2c is thought to be a low affinity, T‐cell independent antibody 28 . This study was unable to determine the binding affinity of IgG2c, although clearly there was some activity.…”

Characterization of two monoclonal antibodies raised in Btkxid mice that recognize phosphorylcholine‐bearing antigens from Trichinella and other helminths

“…Because of the immunodominance of PC-bearing antigens during part of the Trichinella cycle (17,25,26), many hybridoma clones produced by fusion of myeloma cells with B lymphocytes from mice immunized with Trichinella antigens show reactivity against PC-bearing antigens (12,27). However, of all the anti-PC antibodies screened to date, only Mab-2 shows some similarities with our mAbs US1 and US2 produced in Btk xid mice.…”

Part II: Influence of Dimerization of a modified GnRH‐I Peptide Sequence on a Male Antifertility Vaccine

“…However, where IgG2c was a major subclass in TT‐CHWSYGLRPG‐NH 2 treated animals, it was no longer so for the conjugated dimer. As the role of IgG2c has not yet been elucidated, and as our previous results show it has low avidity, this may or may not be relevant 17 , 22 …”