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Biomedical subjects

J Lapeyre

Publications and source records attributed to J Lapeyre.

At least 19 recordsLinked to original sources

Presentation of soluble antigens by mast cells: upregulation by interleukin-4 and granulocyte/macrophage colony-stimulating factor and downregulation by interferon-gamma.

We recently showed that bone marrow-derived mast cells bore MHC class II molecules and could present antigens to specific T cell hybridomas. This article summarizes the effects of purified recombinant cytokines on the expression of MHC class II molecules by mast cells and on their antigen-presenting capacity. Since IL-3 is essential for mast cell growth, all the cytokines were analyzed in the presence of IL-3. IL-3 downregulated the production of Ia molecules, so that mast cells cultured in IL-3 alone had no antigen presenting ability. In contrast, IL-4 and IFN-gamma upregulated the production of MHC class II molecules, while GM-CSF had no effect. The antigen-presenting capacity of IL-4-treated mast cells was substantially enhanced by incubating these cells with GM-CSF for 2 days. GM-CSF enhanced antigen presentation only in combination with IL-4. The activation of mast cells was reversible and could not be repeated. Finally, incubation of IL-4- or IL-4/GM-CSF-treated mast cells with IFN-gamma led to almost complete inhibition of the antigen-presenting function. These findings provide new insights into the regulation of specific allergic responses.

Animals

Antigen-dependent stimulation by bone marrow-derived mast cells of MHC class II-restricted T cell hybridoma.

This paper describes a new role for mast cells as being able to present Ag to immune T cells. A mouse bone marrow-derived mast cell population obtained after 3 wk of culture in a conditioned medium has been shown to express a variety of membrane-associated Ag, including MHC class II and class I Ag, CD23, CD32, high affinity receptor for IgE, and CD4. Expression of MHC class II molecules was up-regulated upon stimulation with LPS but not with IFN-gamma and was down-regulated after exposure of mast cells to IL-3 treatment. We have demonstrated that mast cells were able to present native Ag as well as immunogenic peptides to MHC class II-restricted T cell hybridoma. The inhibition of Ag presentation after mast cells have been treated with ammonia suggests that Ag catabolism in intracytoplasmic compartment as a key step in Ag handling takes place in these cells. The MHC class II molecule is the restricting element for the presentation of OVA and the lambda repressor from bacteriophage lambda to a panel of specific T cell hybridomas, as demonstrated by the blocking effect of anti-MHC class II mAb on the Ag-presenting function. A characteristic feature of mast cells is the generation of a narrower immunogenic peptide repertoire as compared with A20 and LBB 3.4.16, a B lymphoma cell line, and a B cell hybridoma, respectively. This novel function of mast cells brings to a much closer connection inflammatory and immunologic processes and sheds new light on the biology of mast cells and particularly on the specific allergic responses.

Ammonia

Demonstration of idiotypes expressed on basophil-bound IgE antibodies by using anti-idiotype-induced histamine release in grass pollen-allergic patients.

This study was designed to analyse further the idiotypic cross-reactivity between anti-Lol p I murine monoclonal antibodies of IgG isotype and basophil-bound human IgE antibodies from grass pollen-sensitive patients. It was also designed to determine the expression frequency of the idiotypes present on cell-bound IgE. Rabbit anti-idiotypic antisera were produced against idiotypes of three anti-Lol p I monoclonal antibodies (290A-167, 539A-6 and 348A-6) of different specificities. Basophils from 19 patients reacting to Lol p I allergen, as shown by positive skin test reactions and by the presence of serum-specific IgE antibodies (measured by RAST), were challenged with these rabbit anti-idiotypic antibodies and the histamine released was measured. Our data indicate that IgE-borne idiotypes were expressed as follows: (i) co-expression of the three idiotypes in 15% of patients; (ii) co-expression of two idiotypes in 21% of patients; and (iii) expression of a unique idiotype (290A-167) in 42% of patients. Among the three idiotypes, 290A-167 was shown to be a public idiotype since it was expressed in 80% of patients. Fab fragments of anti-idiotypic antibodies could inhibit anti-idiotype-induced histamine release, but optimal conditions varied from one patient to another.

Adult

Heterogeneity of grass pollen allergens (Dactylis glomerata) recognized by IgE antibodies in human patients sera by a new nitrocellulose immunoprint technique.

A new nitrocellulose immunoprint technique has been developed to detect specific antigens or/and allergens present among a heterogeneous solution such as a water-soluble crude extract of a grass pollen (Dactylis glomerata). The antigens are separated by isoelectric focusing (IEF) in an agarose gel and characterized by their isoelectric point (pI). These antigens are transferred and immobilized on a nitrocellulose sheet. They are recognized by the binding of specific antibodies contained in an unfractionated serum to be studied. Finally, the binding of these antibodies is visualized by species- or/and class-specific antibodies themselves labeled by an enzyme or by radioactivity. So one can detect the allergens recognized by the specific serum IgE antibodies and also the other antigens recognized by specific IgG, IgA or IgM antibodies.

Allergens

Magnetic enzyme immunoassay of anti-grass pollen specific-IgE in human sera.

This paper reports a magnetic solid-phase sandwich enzyme immunoassay for specific IgE antibodies in human sera. Crude extracts of grass pollen bound to magnetic polyacrylamide agarose beads were mixed with human serum to be tested. After washing in a magnetic rack, the beads were incubated with the glucose-oxidase-labelled sheep anti-IgE. The enzyme activity associated with the beads was measured by colorimetric assay. Results obtained from sixty-one human sera, as measured by the magnetic enzyme immunoassay, gave a linear correlation coefficient of 0.98 with the values as determined by radio-immunoassay. This procedure, which allows the grass pollen specific IgE in human sera, to be measured, is easy to perform, reproducible and may avoid the use of radioactive compounds.

Antibody Specificity