Human diseases caused by the intracellular bacterium Chlamydia trachomatis include genital tract infections and blinding trachoma. Chlamydial infections are characterized by chronic inflammation and scarring, and development of such complications is thought to be immunologically mediated. In this study, we show that coculture of C. trachomatis (serovar L2) with human blood monocytes induced the production of interleukin-1 (IL-1), an important mediator of inflammation, tissue remodeling, and scarring. IL-1 was produced in response to UV-inactivated elementary bodies containing from 0.1 to 50 ,ig of protein per ml, with a maximal response at 5 to 10 ,ug/ml. IL-1 activity was detected by 6 h of incubation and was maximal by 24 h. Peak levels were maintained throughout 96 h of incubation. Rabbit antibody to human IL-l(a+jp) effectively neutralized the

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The IgG2b-producing MPC 11 mouse myeloma cell line has yielded a number of variants which synthesize heavy chains characteristic of a different immunoglobulin subclass, IgG2a, as previously shown by serology, peptide maps, and assembly profiles. We have studied the Fc regions of the IgG2a protein synthesized by one variant, ICR 9.9.2.1, and of the IgG2b protein synthesized by MPC 11 and compared them to MOPC 173, an IgG2a protein of known sequence. We analyzed the Fc regions of the three immunoglobulins by several analytical techniques, such as immunoelectrophoresis of papain digests, NaDodSo4-polyacrylamide gel electrophoresis analyses of Fc CNBr fragments, and comparative ion-exchange chromatography of radiolabeled tryptic and chymotryptic Fc peptides. In addition, Fc CNBr fragments of the variant gamma2a and MPC 11 gamma2b molecules were isolated and subjected to amino acid analysis and partial sequence determination. From these data, we concluded that the Fc fragment of ICR 9.9.2.1 is most probably identical to that of MOPC 173 and different from the parental gamma2b Fc fragment. A number of residue positions which discriminate between gamma2b and gamma2a sequences are described. In two of three segments sequenced, gamma2b and gamma2a molecules share more identical residues than either shares with another mouse subclass, gamma1.

Tobacco glycoprotein (TGP) is a glycoprotein containing rutin-like polyphenol, groups that is purified from cured tobacco leaves and can be detected in condensates of tobacco smoke. One-third of normal humans have been shown to manifest immediate, IgE-mediated, wheal and flare reactions to an intradermal injection of TGP. Rutin-like moieties are also found in a wide variety of vegetable foods. The possible importance of sensitivity to TGP in the. pathogenesis of the vascular and pulmonary complications of tobacco smoking has stimulated us to study the immune response of mice to TGP and the role of rutin groups in influencing isotype expression. A series of three intradermal injections of TGP elicits a long-lasting IgE antibody response in mice.However, no hemagglutinating antibodies are produced. Similarly, immunization with a rutin derivative of bovine serum albumin stimulates IgE antibodies to bovine serum albumin but little hemagglutinating antibodies. In contrast, mice injected in the same manner with bovine serum albumin produce both IgE and hemagglutinating antibodies. Thus, the rutin moiety is implicated as exerting a regulatory effect on isotype expression by suppressing the production of serum antibodies of isotypes other than IgE. The immunization procedure employed (which involves an initial injection of 100 ,ug of antigen in.phosphate-buffered saline, followed, at monthly intervals, by two intradermal injections of 100 ,ug of antigen precipitated on alum) apparently fails to stimulate the normal "down-regulation" of the IgE response so that a persisting high-titered response is obtained.The regulatory mechanisms involved in isotype expression in general, and in the IgE response in particular, are poorly understood. Genetic factors appear to influence the tendency to produce IgE antibodies (1-5). Antigens whose response is independent of helper T-cell activity, "T-independent antigens," generally do not elicit IgE antibodies (6, 7), whereas parasite infestation (8-10) and certain adjuvants seem to preferentially stimulate an IgE response (11-13). Animal models of the persisting IgE response that is seen in allergic humans have been achieved through various experimental manipulations that probably inactivate suppressor T cells (14)(15)(16)(17).It has been reported (18,19) that one-third-of normal human subjects give immediate, presumably IgE-mediated, wheal and flare skin reactions to tobacco glycoprotein (TGP), a glycoprotein containing rutin (R)-like polyphenol groups, which is purified from cured tobacco leaves. A similar incidence of positive skin tests was observed in smokers and nonsmokers. In addition, when neonate rabbits are immunized with TGP their anti-TGP response is restricted to the IgE class (20 Antigens and Antibodies. TGP was isolated from cured tobacco leaves as described (21). Albumin was obtained from Sigma. R-albumin and R rabbit immunoglobulin (R-RIg) were prepared as described (22). Rabbit anti-TGP serum and rabbit anti-R-albumin serum were prepared as described (18,22)....

12 variant cell lines producing an IgG2a (kappa) immunoglobulin derived via different routes from the IgG2b (kappa) synthesizing MPC 11 were studied. These variants all have the parental MPC 11 idiotype as shown by a radioimmunoassay. A comparison of the variants by charge, peptide maps, and assembly patterns has shown that most of them differ from one another, and some can be grouped. One group consists of three primary variants generated with two mutagenic agents: these three have almost indistinguishable peptide maps. Two other primary variants which arose in a similar fashion differ markedly from each other and from this group. A second group is comprised of the four secondary variants which arose from two short heavy chain producing primary variants. Other secondary variants and the one spontaneously arising variant cannot be grouped. Possible genetic mechanisms such as translocation, expression of previously silent genes and recombination are discussed.