Biomedical subjects

F A Lemonnier

Publications and source records attributed to F A Lemonnier.

76 records · Page 5Linked to original sources

PubMed1982

Analysis of unexpected inhibitions of T lymphocyte proliferation to soluble antigen, alloantigen and mitogen by unfragmented anti-I-Ak or anti-I-E/Ck monoclonal antibodies.

We investigated the capacity of anti-I-Ak and anti-I-E/Ck monoclonal antibodies (m.Ab.) to inhibit T lymphocyte proliferative responses to soluble antigen (Keyhole limpet hemocyanin), alloantigens (H-2 or non-H-2 related) and a mitogen (Concanavalin A). Surprisingly, specific inhibition was observed in all circumstances, and with both anti-I-Ak and anti-I-E/Ck m.Ab., whether the responses tested were I restricted in cell mixing experiments or not. The significance of the inhibition by anti-Ia m.Ab. of non-Ia-restricted responses is still not completely understood. These results, however, strongly suggest that in vitro inhibition by anti-Ia antibodies of T cell proliferative responses does not necessarily indicate I restriction of the presentation to T lymphocytes of the corresponding antigen.

Animals↗

PubMed1981

KLH-specific, I-E/C-restricted clones of proliferating T lymphocytes.

The recognition of keyhole limpet hemocyanin by a substantial proportion of proliferating clones of murine T lymphocytes was found to be restricted by the I-E/Ck molecule, which is a combinatorial product of genes located in the I-A (Ae) and I-E/C (E alpha) subregions of the murine major histocompatibility complex. The respective roles of the Ae (polymorphic) and E alpha (oligomorphic) gene products in the expression of the structures which are used as restriction elements by these T-cell clones was analyzed by mating parental strains unable to present the antigen and bearing selected Ae and E alpha alleles. Efficient complementation for antigen presentation was found to require the expression by accessory cells of the Aek-gene product, whereas all E alpha allelic molecules were functionally equivalent. These results (a) indicate that the immunoregulatory role of I-region gene products, initially described for molecules selected for their limited number of antigenic epitopes, also applies to complex multiepitopic antigens; (b) illustrate the advantage which results from the diversity of the Ia molecules expressed by accessory cells for the development of potent immune responses; and (c) suggest that a correlation might exist between the degree of polymorphism of a given family of H-2 allelic molecules and their ability to be used as restriction elements for antigen recognition by T lymphocytes.

Alleles↗

PubMed1981

Cell surface fixation of alloantigen bearing plasma vesicles in the presence of polyethylene glycol.

The fixation of plasma vesicles at the surface of intact mouse spleen or tumor cells was studied in order to introduce the foreign alloantigens of the vesicles into the plasma membrane of these cells. A 3-6-fold increase of fixation of radioiodinated vesicles was obtained when cells and vesicles were incubated in the presence of polyethylene glycol 1500 (PEG 1500). The fixation of vesicles on the surface of cells was demonstrated by scanning electron microscopy. Cells treated with vesicles in the presence of PEG acquired the corresponding membrane alloantigens, as demonstrated by cellular binding radioimmunoassay. However, sensitivity to antibody-dependent lysis was obtained only when vesicle fixation was achieved in the presence of both wheat germ agglutinin and polyethylene glycol. The introduction of foreign alloantigens in the plasma membrane of the treated cells might help to define the functional properties of these molecules.

Animals↗

PubMedDate not supplied

Antigenicity and immunogenicity of an intracellular delivery system of major histocompatibility complex class I epitopes that bypasses proteasome processing.

The development of a cell-free synthetic vaccine to induce an effective cytotoxic T lymphocyte response is an important challenge in T-cell--mediated immunity. Because standard vaccinations with nominal epitopes were found to be only partially effective in vivo, the authors suggest an alternative strategy: the delivery of epitopes directly to the cell cytosol in a proteasome bypass mechanism of processing. Two model peptides, the presentation level on the cell surface of which can be directly assessed, were conjugated via a cross-linker to an internalization peptide derived from an antennapedia homeobox protein. The linker was designed to undergo spontaneous hydrolysis, after which the epitope is subsequently released. The conjugates were shown to enter RMA and P815 cells, where the epitopes were released mainly in cytosol and endogenously loaded on the major histocompatibility complex class I molecules to be presented on the cell surface. Concomitant inhibition of proteasome activity by MG132 significantly increased the presentation level of both model peptides, indicating proteasome-independent processing. This phenomenon was exploited to enhance the immunogenicity of the conjugates. Conjugates were emulsified with MG132 in incomplete Freund's adjuvant and injected into mouse footpads. Analysis of the draining lymph nodes indicated an increase in the percentage of both CD4+ and CD8+ lymphocytes. In vitro cytolytic assays implied significant, albeit moderate, priming only when the proteasome inhibitor was administered with the conjugate. This approach may be useful for the development of efficient synthetic cell-free vaccines.

Animals↗