Universitè Catholique De Louvain

Institut National De La Sante Et De La Recherche Medicale

Biotransplant, Inc.

Herve Bazin

Dominique Latinne

Ruth A Kaplan

Mary E White-Scharf

Thomas Kieber-Emmons

Christina E Postema

Jean P Klein

Fabienne Ackermans

Robert Frank

Dominque Latinne

Dominuque Latinne

The present invention relates to a LO-CD2a antibody and methods of using such antibodies or molecules that bind to the same epitope (or a portion thereof) to prevent and inhibit an immune response in human patients, preferably, where the immune response is mediated by the activation and proliferation of T cells or natural killer cells. The administration of an effective amount of the LO-CD2a antibody to a human patient will prevent or inhibit graft rejection, graft versus host disease or autoimmune disease.

Composition comprising the LO-CD2a antibody

Although the mechanism of induction of apoptosis through antibody dependent cellular cytotoxicity (ADCC) mediated by NK cells is well understood, little is known about the fate of the reactive NK cells. Nevertheless, it has been shown that NK cells previously activated by IL-2, but not naive NK cells, died by apoptosis after Fc&ggr;RIIIa crosslinking, or after engagement in cytolytic functions. It is demonstrated that apoptosis of naive NK cells is also observed after stimulation with a rat IgG2 anti CD2 mAb (LO-CD2 /BTI-322) or anti HLAI (LO-HLA-1)mAb. The NK apoptosis is rapid (within minutes), Fas-ligand and mRNA synthesis independent and does not require a cell contact. The intracellular mechanism of NK cell apoptosis is calcium, PKC and PLA2 dependent but calcineurin and P13 kinase independent. We suggest that NK cell apoptosis results from the crosslinking on the same cell surface of CD2 or HLA-I molecules and Fc&ggr;RIIIa that exhibits a high affinity for the rat IgG2 isotype. The clinical application of these experiments are discussed.

Apoptosis of naive human NK cells by crosslinking of their Fc&ggr;RIIIa molecules with a rat IgG2b (LO-CD2a/BTI-322) or its IgG1 humanized monoclonal antibody

Methods of inhibiting T cell mediated immune responses with humanized

Methods of inhibiting T-cell medicated immune responses with

LO-CD2a antibody and uses thereof for inhibiting T cell activation and

The conjugate according to the invention is constituted by a wall adhesin of Streptococcus mutans, of a proteinic nature, capable of binding the components of saliva, or an active fraction of such a protein, covalently coupled to a Streptococcus mutans polysaccharide, or to a fraction of such a polysaccharide. Preferably, the adhesin is constituted by a single polypeptide chain having a molecular weight of about 74,000; it is common to the different serotypes of Streptococcus mutans where it has a crossed antigenicity; and it is capable of interacting with the salivary glycoproteins and polysaccharide derived from the same serotype of S. mutans, particularly serotype f. Use for the preparation of immunogenic compositions, particularly for the preparation of vaccines against dental caries.

Conjugate constituted from a wall adhesin of S. mutans of proteinic

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Brussels, Belgium

Herve Bazin