In common with other taeniid cestodes, host or host-like proteins, especially immunoglobulins, occur on the surface and in the cyst fluid of Taenia crassiceps metacestodes. Here, several approaches have been used to determine the origin of the immunoglobulins present on the tegument. Indirect IFAT showed that IgG was almost totally lost from the surface of bladders after 6 days culture in vitro. There was a rapid reacquisition of immunoglobulins following incubation of the cultured metacestodes with either normal mouse serum or mouse anti-T. crassiceps antiserum. Immunoprecipitation of in vitro translation products and biosynthetically labelled T. crassiceps proteins with a panel of anti-IgG antisera failed to positively identify any molecule with homology to mammalian immunoglobulins. These results suggest strongly that the immunoglobulins located on the surface of T. crassiceps are of host rather than parasite origin. The occurrence of a relatively low abundance receptor in the surface of the bladders, which binds non-specific host immunoglobulin, together with surface-bound specific anti-T. crassiceps antibodies can account for the presence of these host proteins. Freshly obtained bladders and metacestodes cultured in vitro for 6 days were transplanted into naive mice and the survival and development of the resulting parasites compared. In some individual mice there was a decrease in the number and volume of metacestodes and an increase in encapsulated parasites arising from cultured bladders. This was probably not related to the loss of host immunoglobulins from the parasite surface during culture as the reacquisition of these proteins after transplantation is likely to be far more rapid than any immune response could evoke in a naive host.

The presence of antigenic carbohydrate epitopes shared by Biomphalaria glabrata as well as by the sporocysts and miracidia representing snail-pathogenic larval stages of Schistosoma mansoni was assayed by immunohistochemical staining of paraformaldehyde-fixed tissues. To this end, both polyclonal rabbit antiserum raised against soluble egg antigens (SEA) of S. mansoni and monoclonal antibodies recognizing the carbohydrate epitopes LDN [GalNAc(β1-4)GlcNAc(β1-)], F-LDN [Fuc(α1-3)GalNAc(β1-4)GlcNAc(β1-)], LDN-F [GalNAc(β1-4)[Fuc(α1-3)]GlcNAc(β1-)], LDN-DF [GalNAc(β1-4)[Fuc(α1-2)Fuc(α1-3)]GlcNAc(β1-)] and Lewis X [Gal(β1-4)[Fuc(α1-3)]GlcNAc(β1-)] were used. Intriguingly, anti-SEA serum as well as anti-F-LDN antibodies displayed significant binding in the foot region, anterior tissue and the hepatopancreas of uninfected snails, whereas the Lewis X epitope was only weakly detectable in the latter tissue. In contrast, increased binding of antibodies recognizing LDN, LDN-F and LDN-DF was observed in infected snail tissue, in particular in regions involved in sporocystogenesis, in addition to an enhanced binding of anti-SEA serum and antibodies reacting with F-LDN. A pronounced expression of most of these carbohydrate antigens was also observed at the surface of miracidia. Hence, the detection of shared carbohydrate determinants in uninfected snail tissue, sporocysts and miracidia may support the hypothesis of carbohydrate-based molecular mimicry as a survival strategy of S. mansoni.

Molecular mimicry between streptococcal and human proteins has been proposed as the triggering factor leading to autoimmunity in rheumatic fever (RF) and rheumatic heart disease (RHD). This article summarises studies on genetic susceptibility markers involved in the development of RF/RHD. It also focuses on the molecular mimicry in RHD mediated by the responses of B and T cells of peripheral blood, and T cells infiltrating heart lesions, against streptococcal antigens and human tissue proteins. The molecular basis of T-cell recognition is assessed through the definition of heart-crossreactive antigens. The production of cytokines from peripheral and heart-infiltrating mononuclear cells suggests that T helper 1 (Th1)-type cytokines are the mediators of RHD heart lesions. An insufficiency of interleukin 4 (IL-4)-producing cells in the valvular tissue might contribute to the maintenance and progression of valve lesions.

Patients with the autoimmune rheumatic disease systemic lupus erythematosus (SLE or ‘lupus’) develop a wide variety of clinical and serological manifestations including the presence of antibodies to double-stranded DNA (dsDNA), which are often diagnostic and potentially pathogenic. In this review, we have examined the links between the structure and function of anti-dsDNA antibodies, emphasising their clinical associations. We have also reviewed studies involving animal models, the analysis of human antibody sequences and studies of, and using, computer modelling and crystal structure.

In addition to being a component of the large ribosomal subunit, ribosomal protein L20 of Escherichia coli also acts as a translational repressor. L20 is synthesized from the IF3 operon that contains three cistrons coding for IF3, and ribosomal proteins L35 and L20. L20 directly represses the expression of the gene encoding L35 and the expression of its own gene by translational coupling. All of the cis-acting sequences required for repression by L20, called the operator, are found on an mRNA segment extending from the middle of the IF3 gene to the start of the L35 gene. L20-mediated repression requires a long-range base-pairing interaction between nucleotide residues within the IF3 gene and residues just upstream of the L35 gene. This interaction results in the formation of a pseudoknot. Here we show that L20 causes protection of nucleotide residues in two regions of the operator in vitro. The first region is the pseudoknot itself and the second lies in an irregular stem located upstream of the L35 gene. By primer extension analysis, we show that L20 specifically induces reverse transcriptase stops in both regions. Therefore, these two regions define two L20-binding sites in the operator. Using mutations and deletions of rpmI’-‘lacZ fusions, we show that both sites are essential for repression in vivo. However L20 can bind to each site independently in vitro. One site is similar to the L20-binding site on 23S rRNA. Here we propose that L20 recognizes its mRNA and its rRNA in similar way.

Patients with systemic autoimmune disorders produce autoantibodies against sequence-specific conformational RNA epitopes on U1 snRNA, 28S rRNA, and transfer RNAs. The molecular basis for immunological reactivity with these highly abundant and stable RNAs is not understood. Here, we report the existence of discrete RNA epitopes in messenger RNAs that are generally less abundant and less stable than snRNAs and tRNAs. An iterative selection and amplification procedure using pooled autoimmune patient sera identified immunoreactive mRNA species. Following deconvolution of the pools to identify the reactive sera, several mRNAs recognized by these autoantibodies were cloned and sequenced. Detailed analysis using one particular serum indicated reactivity against the messages encoding alternative splicing factor (ASF/SF2) and calmodulin. Deletion and site-directed mutagenesis determined that an epitope recognized by this serum is located in a 17-base stem-loop structure common to both messages. This serum was then used to immunoprecipitate native mRNAs encoding ASF/SF2 and calmodulin from total HeLa cell RNA. Our results demonstrate that despite its low abundance and instability, messenger RNA is capable of reacting with autoantibodies generated during an autoimmune response. These data are consistent with direct presentation as a model to explain the generation of RNA conformation-specific autoantibodies.

Recent developments in parasite immune evasion and exploitation are reviewed with special reference to the papers presented in this volume. Parasites, broadly defined, of animals with good immune responses have evolved many strategies that adapt them to survive and reproduce. These strategies may be passive, or may involve active intervention with host immune regulation, and can be categorized as immune evasion, immune exploitation and molecular piracy. The concept of immune evasion began with Paul Ehrlich's demonstration of antigenic variation in African trypanosomes and was reinforced by later ideas on molecular mimicry. Molecular mimicry is updated in the light of recent discoveries about degeneracy and plasticity of TCR/MHC-peptide recognition. Possible connections between two of its postulated consequences, evasion and autoimmunity, are discussed. Another putative consequence of molecular mimicry, host antigenic polymorphism, is also updated. The concept of exploitation of host immune responses by parasites has been reinforced by new data on its first known examples, especially the immune dependence of schistosome egg excretion. Newer examples include use of host cytokines as parasite growth factors, virokines, viroreceptors and helminth pseudocytokines. Finally, questions of host gene capture by viruses and possible horizontal gene transfer between host and parasite mediated by retroviruses are examined. The latter is compared with molecular conservation as a source of molecular mimicry and other aspects of host–parasite coevolution.

We have previously reported that the mechanisms of neuromyopathic damage induced by Trypanosoma cruzi are mediated by T cells and are parasite-strain dependent. In the present study our aim was to determine whether the humoral response against muscle and nervous system is also parasite-strain dependent. Of the sera from mice infected with RA and CA-I T. cruzi strains, 93% reacted against antigens of the nervous system (sciatic nerve, spinal cord and brain). No differences in the ability to recognize heart antigens were found between RA (48%) and CA-I (63%) antisera. Reactivity against skeletal muscle was only relevant in anti-CA-I sera at 270 days post-infection. Each of the antisera assayed in Western blots developed a particular antigenic pattern, but 3 antigens in the nervous system of molecular weight 48, 60 and 70 kDa were detected by 42, 28 and 23% of the sera, respectively. On the other hand, deposits of IgG were observed at the interstitial matrix in sciatic nerve and as endomisial and sarcolemmal patterns in skeletal muscle by IFAT for both RA and CA-I antisera. Absorption of sera with parasite antigens did not abolish the autoreactivity. Our results suggest that major serum autoreactivity from T. cruzi-infected mice is not parasite-strain dependent and does not arise from molecular mimicry.