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B Frangoulis

Publications and source records attributed to B Frangoulis.

10 recordsLinked to original sources
PubMed1992

Localization of the conformational alteration of MHC molecules induced by the association of mouse class I heavy chain with a xenogeneic beta 2-microglobulin.

Changes in the antigenicity of major histocompatibility complex (MHC) class I molecules resulting from the association of bovine beta 2-microglobulin (beta 2-m) with mouse class I heavy chains were investigated. Mice (H-2b) were immunized with syngeneic Concanavalin A (Con A) blasts induced in the presence of fetal calf serum (FCS) in conditions allowing exchange between mouse and bovine beta 2-microglobulin (beta 2-m). Spleen cells from hyperimmunized mice were fused with myeloma cells and two monoclonal antibodies which required for their reactivity the presence of FCS have been further studied. One of them (CAB 297) recognized a determinant of bovine beta 2-m which is present on free molecules in solution as well as when they are associated with either mouse or bovine class I heavy chains. In contrast, the second monoclonal antibody (CBB 70) did not react with free bovine beta 2-m molecules, nor with beta 2-m associated with bovine class I heavy chains. It did react with cells of some H-2 haplotypes (b, f, p and r) but only when their class I heavy chains are associated with bovine or with human beta 2-m. Therefore, expression of the CBB 70 defined antigenic determinant requires both xenogeneic beta 2-m and class I heavy chain of a given H-2 molecule. In order to precisely localize the antigenic determinant defined by this monoclonal antibody and therefore the region altered by the association of class I heavy chain with xenogeneic beta 2-m, we made use of exon shuffled class I molecules. The results indicate that changes induced by the association of bovine beta 2-m with H-2 class I heavy chain affect the conformation of the alpha 2 domain. These studies illustrate that MHC class I molecules exhibit a considerable conformational flexibility which could influence their ability to bind and present various peptides to the T-cell receptor.

Animals↗
PubMed1991

Recognition of HLA-B27 by mouse cytotoxic T-cell clones: a transgenic mouse model.

As a basis for the characterization of mouse T cells involved in the recognition of xenogeneic HLA molecules, a panel of HLA-B27-reactive cytotoxic T-cell clones was generated upon stimulation by cells from HLA-B27-transgenic mice. The HLA-B27-induced T-cell response was found to comprise two categories of clones: some recognizing HLA-B27 independent of H-2 molecules expressed by the target cells (unrestricted clones), others recognizing HLA-B27 in an H-2-restricted manner. The unrestricted clones exhibited diverse specificities, as judged from their various cross-reactivities with other xenogeneic (HLA) or allogeneic (H-2) molecules. In addition, although most of the unrestricted clones were able to react with both mouse and human HLA-B27-transgenic mice. The HLA-B27-induced T-cell which reacted only with HLA-B27-positive mouse, and not human cells. These findings illustrate that both H-2-restricted and unrestricted T cells with diverse specificities contribute to HLA-B27-xenorecognition.

Animals↗
PubMed1989

Clonal anergy induced in mature V beta 6+ T lymphocytes on immunizing Mls-1b mice with Mls-1a expressing cells.

Tolerance to self-antigens has been shown to develop during ontogeny as a result of the clonal deletion of self-reactive T cells. Tolerance, or better 'nonresponsiveness', to specific antigens can also be induced in adult animals but the mechanism(s) involved are not well understood. Most murine T-helper cells that express the V beta 6 T-cell receptor gene segment are specific for Mls-1a antigens. We have therefore been able to use an anti-V beta 6 monoclonal antibody to follow the fate of Mls-1a specific T cells in adult Mls-1b mice made specifically unresponsive to Mls-1a. We show that the induced unresponsiveness is not due to clonal deletion, but rather to clonal anergy. The anergic V beta 6 T-helper cells express IL-2 receptors and undergo limited blastogenesis in vitro upon stimulation, but do not produce IL-2, in marked contrast to V beta 6 cells from naive mice. Our data appear to represent an in vivo correlate for the induction of anergy that has been observed in T-cell lines in vitro.

Animals↗
PubMed1989

Alternative T cell receptor gene usage induced by self tolerance.

Ab-restricted, H-Y-specific T cell clones from C57BL/6 mice were found to use predominantly V beta 6 T cell receptor genes, conferring Mls-1a reactivity. However, the expression of Mls-1a as a self antigen in (DBA/2 x C57BL/6)F1 mice did not turn these mice into nonresponders to H-Y. Instead of V beta 6, they used other T cell receptor genes in this response. Thus, self tolerance appears to bias the repertoire of T cell receptor genes used in response to foreign antigens, without necessarily impairing the immune responsiveness to these antigens.

Animals↗
PubMed1988

Immune response to H-2 class I antigens on platelets. I. Immunogenicity of platelet class I antigens.

Purified allogeneic murine platelet suspensions were found unable to induce primary anti-H-2 class I antibody or T cell proliferative responses. In contrast, the same platelet suspensions could elicit secondary anti-class I responses. The secondary responses were not due to contaminating leucocytes. Possible explanations, the lack of acolyte determinants (class II or non- H-2) on platelets or inappropriate layout and/or structure of their class I antigens, are discussed. These findings emphasize the importance of sufficient leucocyte depletion before platelet transfusion in the human.

Animals↗
PubMed1988

Immune response to H-2 class I antigens on platelets. II. Specific decrease of H-2 class I-specific antibody response induced by treatment with allogeneic platelets.

Mice pretreated with injections of allogeneic platelets were found to mount a decreased antibody response upon challenge by lymphocytes of the same donor strain. This decrease was mediated by platelets themselves, and not by leucocytes and red cells contaminating the platelet suspension. It affected specifically antibodies reactive with H-2 class I antigens present on donor platelets. This phenomenon may be related to the lack of class II or some non-H-2 antigens on platelets, and/or to properties of their class I antigens (soluble molecules adsorbed from the plasma). These findings emphasize the potential usefulness of purified platelet transfusions preceding organ transplantation in man.

Animals↗
PubMedDate not supplied

Anti-MHC immunity detected prior to intentional alloimmunization. IV. Natural monoclonal H-2-specific antibodies.

Naturally occurring H-2-specific antibodies can be detected rather frequently in sera of non-alloimmunized mice by sufficiently sensitive techniques (Cerny-Provaznik et al., 1985a; Cerny-Provaznik & Ivanyi, 1985). In this report, we summarize our experiences with the preparation of monoclonal anit-H-2 antibodies obtained from hybridization experiments from non-alloimmunized mice. From a total of 30 spleen cell hybridization experiments, we could isolate only four anti-H-2 monoclonal antibodies (mAB). Two of the mAB are described in this report. Monoclonal antibody By-2 is anti-Kf and mAB By-3 is anti-Db, Ds. We investigated which conditions favour the isolation of monoclonal H-2-specific antibodies from non-alloimmunized mice. The presence of naturally occurring serum antibodies, the age of the spleen donor mouse or non-specific B cell stimulation were not critical for the isolation of natural anti-H-2 mAB. We hypothesise that the 'natural' H-2-specific antibodies represent compartments of the B cell repertoire which were triggered by modified or aberrant self-MHC expression.

Animals↗
PubMedDate not supplied

High frequency of Mlsa-reactivity among Ab-restricted, H-Y-specific T cell clones.

A high frequency (80%) of Ab-restricted, H-Y-specific T cell clones, but not of Ab-restricted LDH-B-specific T cell clones, was found to be Mlsa-reactive. This reactivity could be inhibited by class II (A and E)-specific antibodies, and required an E-positive stimulator cell. The proliferation was also blocked by T cell receptor-specific and by CD4-specific antibodies. Possible interpretations of these findings are discussed.

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