Presence of anti-Trypanosoma cruzi antibodies in the sera of mice with experimental autoimmune myocarditis

Summary The existence of antigens shared in common byT. cruzi and heart muscle cells is suggested by the presence of antibodies binding to the parasite surface in the serum of mice with autoimmune myocarditis induced by immunization with syngeneic heart antigens.     

Alloantigens directed by the SL-A region control the mixed lymphocyte reaction in swine]

Immunizations between a pig bearing a recombined SL-A haplotype and related animals revealed serological defined antigens under the MLR region control. These antigens seemed to be carried by all types of lymphocytes so far studied, but with large quantitative differences. The blood nonadherent on nylon fiber lymphocytes carried very few antigens and platelets none at all. The data are compatible with the assumption that these newly discovered antigens are equivalent to the mouse Ia antigens.     

Alternative pathways for MHC class I presentation: a new function for autophagy

The classical view that endogenous antigens are processed by the proteasome and loaded on MHC class I molecules in the endoplasmic reticulum, while exogenous antigens taken up by endocytosis or phagocytosis are degraded and loaded on MHC class II in lysosome-derived organelles, has evolved along with the improvement of our understanding of the cell biology of antigen-presenting cells. In recent years, evidence for alternative presentation pathways has emerged. Exogenous antigens can be processed by the proteasome and loaded on MHC class I through a pathway called cross-presentation. Moreover, endogenous antigens can be targeted to lytic organelles for presentation on MHC class II through autophagy, a highly conserved cellular process of self-eating. Recent evidence indicates that the vacuolar degradation of endogenous antigens is also beneficial for presentation on MHC class I molecules. This review focuses on how various forms of autophagy participate to presentation of these antigens on MHC class I.     

Molecular recognition of microbial lipid-based antigens by T cells

The immune system has evolved to protect hosts from pathogens. T cells represent a critical component of the immune system by their engagement in host defence mechanisms against microbial infections. Our knowledge of the molecular recognition by T cells of pathogen-derived peptidic antigens that are presented by the major histocompatibility complex glycoproteins is now well established. However, lipids represent an additional, distinct chemical class of molecules that when presented by the family of CD1 antigen-presenting molecules can serve as antigens, and be recognized by specialized subsets of T cells leading to antigen-specific activation. Over the past decades, numerous CD1-presented self- and bacterial lipid-based antigens have been isolated and characterized. However, our understanding at the molecular level of T cell immunity to CD1 molecules presenting microbial lipid-based antigens is still largely unexplored. Here, we review the insights and the molecular basis underpinning the recognition of microbial lipid-based antigens by T cells.     

Antigen presentation by CD1 molecules and the generation of lipid-specific T cell immunity

It is now well demonstrated that the repertoire of T cells includes not only cells that recognize specific MHC-presented peptide antigens, but also cells that recognize specific self and foreign lipid antigens. This T cell recognition of lipid antigens is mediated by a family of conserved MHC class I-like cell surface glycoproteins known as CD1 molecules. These are specialized antigen-presenting molecules that directly bind a wide variety of lipids and present them for T cell recognition at the surface of antigen-presenting cells. Distinct populations of T cells exist that recognize CD1-presented lipids of microbial, environmental or self origin, and these T cells participate in immune responses associated with infectious, neoplastic, autoimmune and allergic diseases. Here we review the current knowledge of the biology of the CD1 system, including the structure, biosynthesis and trafficking of CD1 molecules, the structures of defined lipid antigens and the types of functional responses mediated by T cells specific for CD1-presented lipids.     

Profile identification of disease-associated humoral antigens using AMIDA, a novel proteomics-based technology

We describe AMIDA (autoantibody-mediated identification of antigens), a novel target identification technology based on the immunoprecipitation of disease-specific antigens by autologous serum antibodies followed by two-dimensional electrophoretic separation, and their identification via mass spectrometry. Twenty-seven potential carcinoma antigens were identified including proteins of hitherto unknown function. Validation of one of the identified antigens, cytokeratin 8, revealed its de novo expression in hyperplastic tissue, gradual overexpression with increasing malignancy, and ectopic localization on the cell surface. Furthermore, a strong prevalence of CK8-specific antibodies occurred in the serum of cancer patients already at early disease stages. In situ hybridization for one marker of unknown function, KIAA1273/TOB3, demonstrated its strong overexpression in head and neck carcinomas, thus making it a likely tumor antigen candidate. Eventually, AMIDA could foster significant improvements for the diagnosis and therapy of human diseases eliciting a humoral immune response, and allows for the rapid identification of new target molecules.Received 30 January 2004; received after revision 3 March 2004; accepted 8 March 2004     

HLA-DRw7 in psoriasis vulgaris

40 unrelated patients with Psoriasis vulgaris were studied for their HLA-A, B and DRw antigen phenotypes. All underwent a skin biopsy to confirm diagnosis. Like most of the authors, we observed an increase in B13 and B17 antigens (17,50 and 25%) whereas in the healthy population the percentage was (5 and 6,02%) respectively. The strong increase in DRw7 suggests that psoriasis vulgaris was associated with DRw7 antigens, with an unbalanced linkage between the B13 and DRw7 antigens and between the B17 and DRw7 antigens.     

Comparison of cutaneous hyperemia in cattle elicited by larvae ofBoophilus microplus and by prostaglandins and other mediators

Summary Blood flow has been measured in bovine skin following the injection of tick antigens and a number of pharmacological mediators; including histamine, prostaglandins and slow reacting substance of anaphylaxis. The greates increase in blood flow (20 times normal) was recorded with tick antigens and with prostaglandin F2. This mediator may therefore influence blood flow during immune reactions to ticks and during the rapid ingestion of blood by the ticks.Acknowledgments. This work was supported by the Australian Meat Research Committee. We would like to thank J. M. Gough for her technical assistance.     

Presence of serum proteins in submaxillary duct perfusate

The secretory activity of the main excretory duct of rat submaxillary gland was investigated by the technique of luminal perfusion. Immunologic studies of the perfusate revealed the presence of serum antigens and the absence of intrinsic submaxillary gland antigens. It is suggested that the submaxillary duct permits passive transport of serum proteins to saliva from serum.     

Presence of serum proteins in submaxillary duct perfusate

Summary The secretory activity of the main excretory duct of rat submaxillary gland was investigated by the technique of luminal perfusion. Immunologic studies of the perfusate revealed the presence of serum antigens and the absence of intrinsic submaxillary gland antigens. It is suggested that the submaxillary duct permits passive transport of serum proteins to saliva from serum.     

Absence of relationship between erythrocyte and viral antigen expressed on the surface of chick erythrocytes]

Anti-gs antisera were tested on embryo and adult Chick erythrocytes. Specific immunsera directed against Chick embryo or adult erythrocyte antigens have been tested on Hamster cell lines infected with the Rous virus. Results demonstrate that the erythrocyte and viral antigens are different.     

Babesia bovis: the effect of acute inflammation and isoantibody production in the detection of babesial antigens

Summary Immunoblots ofBabesia bovis antigen contain dominant antigens which react not only with antisera toB. bovis but with sera from naive calves recovering from an acute inflammatory reaction. It seems likely these antigens are from the host rather than the parasite.     

Zur Immunchemie der Klebsiella-Antigene

Summary The capsular (K) and somatic (O) antigens of 72 Klebsiella-type strains were isolated and investigated with respect to their chemical composition and their serological behaviour. The K antigens were found to be acidic heteropolysaccharides carrying serological K specificity. The O antigens are lipopolysaccharides which are O group-specific.     

Inhibition of IgM antibody-mediated aggregation of Trypanosoma gambiense in the presence of complement.

This paper deals with the immune reaction between Trypanosoma gambiense and monoclonal IgM mouse antibody at equivalence with or without rabbit complement. Antibody-mediated trypanosome clumps formed in the absence of complement, and were readily dissociated by complement to become free. In the presence of complement, on the other hand, T. gambiense were not aggregated by the antibody. Free parasites adhered readily to cultured peritoneal macrophages. Complement-mediated dissociation of the clumped trypanosomes in the equivalence area released a large number of previously bound surface antigens. These antigens were capable of binding again to fresh IgM antibody. Experimental results further indicated that the complement system caused a functional alteration, changing the multivalent nature of the IgM antibody in the immune complex into a univalent one. This phenomenon is of great advantage to the infected host in clearing pathogens in vivo, as it allows more antibodies to attach to trypanosomes and subsequently initiate complement activity.     

Immunological and radioimmunological studies of membrane antigen(s) from human breast carcinomas and non-tumoral breast tissues. I.

Summary The authors extracted and partially purified a pool of antigens from primary breast carcinomas. The antigens responded to anti-CEA antibody in a radioimmunoassay (R. I. A.) and were not detected in non-tumoral breast tissues used as controls. Antisera were obtained by immunizing rabbits.The authors want to express their appreciation to Dr Sergio Orefice, Prof. Carlo Mor and Dr Luisa Amante for their collaboration.     

Induction of heart alterations by immunization with subcellular fractions from Crithidia fasciculata

Immunization of mice with subcellular fractions of C. fasciculata led to myocarditis and electrocardiographic alterations similar to those induced by immunization with T. cruzi, the etiological agent of Chagas' disease, suggesting the presence of similar cardiotoxic antigens in both trypanosomatid flagellates.     

Inhibition of IgM antibody-mediated aggregation ofTrypanosoma gambiense in the presence of complement

This paper deals with the immune reaction betweenTrypanosoma gambiense and monoclonal IgM mouse antibody at equivalence with or without rabbit complement. Antibody-mediated trypanosome clumps formed in the absence of complement, and were readily dissociated by complement to become free. In the presence of complement, on the other hand,T. gambiense were not aggregated by the antibody. Free parasites adhered readily to cultured peritoneal macrophages. Complement-mediated dissociation of the clumped trypanosomes in the equivalence area released a large number of previously bound surface antigens. These antigens were capable of binding again to fresh IgM antibody. Experimental results further indicated that the complement system caused a functional alteration, changing the multivalent nature of the IgM antibody in the immune complex into a univalent one. This phenomenon is of great advantage to the infected host in clearing pathogens in vivo, as it allows more antibodies to attach to trypanosomes and subsequently initiate complement activity.     

Mechanistic insights into the efficacy of cell penetrating peptide-based cancer vaccines

Immunotherapies are increasingly used to treat cancer, with some outstanding results. Immunotherapy modalities include therapeutic vaccination to eliminate cancer cells through the activation of patient’s immune system against tumor-derived antigens. Nevertheless, the full potential of therapeutic vaccination has yet to be demonstrated clinically because many early generation vaccines elicited low-level immune responses targeting only few tumor antigens. Cell penetrating peptides (CPPs) are highly promising tools to advance the field towards clinical success. CPPs efficiently penetrate cell membranes, even when linked to antigenic cargos, which can induce both CD8 and CD4 T-cell responses. Pre-clinical studies demonstrated that targeting multiple tumor antigens, even those considered to be poorly immunogenic, led to tumor regression. Therefore, CPP-based cancer vaccines represent a flexible and powerful means to extend therapeutic vaccination to many cancer indications. Here, we review recent findings in CPP development and discuss their use in next generation immunotherapies.     

Malaria vaccine

Summary Among infectious diseases caused by protozoa, malaria is still the greatest killer of children. Mortality in adults living in endemic areas is significantly lower because they frequently acquire partial or complete immunity to the major pathogen,Plasmodium falciparum. This natural protection indicates that vaccination may be possible, and the first candidate antigens were cloned with the use of human immune sera as probes. Genetic and biochemical analysis of the parasite proteins revealed that they are polymorphic, and frequently gene sequences were discovered which were specific for a particular parasite isolate, which eliminated most antigens for purposes of vaccine development. The most promising candidate antigens today are the major surface proteins of sporozoites and blood stage parasites. However, the immune response against those is not sufficient for complete protection, and additional, intensive research is necessary to identify new molecules to be included in a vaccine cocktail against malaria. The current spread of the disease due to increasing drug resistance of parasites and mosquito vectors emphasizes the urgent need for a vaccine.