Abstract: Isolated ligands which bind a molecule expressed on the surface of T cells and induce antigen specific apoptosis in activated T cells are disclosed. Preferably, the T cell surface molecule is CTLA4 and the ligand is a monoclonal anti-CTLA4 antibody that binds to an epitope of CTLA4 distinct from the binding sites of B7-1 and B7-2. Upon binding of the antibody to CTLA4 on an activated T cell, in the presence of an antigenic signal, antigen specific apoptosis is induced. The invention also describes a novel natural CTLA4 ligand, distinct from B7-1 and B7-2, which mediates induction of apoptosis. Pharmaceutical compositions of anti-CTLA4 antibodies or other isolated CTLA4 ligands which can be administered to subjects to induce T cell apoptosis, thereby clonally deleting antigen specific T cells, such as alloreactive T cells in transplantation situations or autoreactive T cells in autoimmune disorders, are also disclosed.

Abstract: Isolated ligands which bind a molecule expressed on the surface of T cells and induce antigen specific apoptosis in activated T cells are disclosed. Preferably, the T cell surface molecule is CTLA4 and the ligand is a monoclonal anti-CTLA4 antibody that binds to an epitope of CTLA4 distinct from the binding sites of B7-1 and B7-2. Upon binding of the antibody to CTLA4 on an activated T cell, in the presence of an antigenic signal, antigen specific apoptosis is induced. The invention also describes a novel natural CTLA4 ligand, distinct from B7-1 and B7-2, which mediates induction of apoptosis. Pharmaceutical compositions of anti-CTLA4 antibodies or other isolated CTLA4 ligands which can be administered to subjects to induce T cell apoptosis, thereby clonally deleting antigen specific. T cells, such as alloreactive T cells in transplantation situations or autoreactive T cells in autoimmune disorders, are also disclosed.

Abstract: The present invention provides compositions and methods useful for promoting or reducing T-cell trafficking to a target tissue. Also provided are compositions and methods useful for promoting or inhibiting antigen-presenting cell (APC) activation. The invention is related to discovery of functional characteristics of TIM-3, a molecule that is preferentially expressed on the surface of Th1 cells. The methods are useful for treating disorders including cancer, infectious disease, allergy, asthma, and autoimmune disease.

Abstract: The present invention relates to methods and products for immunotherapy resulting in the stimulation of T-cell proliferation. The products of the invention are peptides that bind to CTLA-4 and co-stimulate the proliferation of T-cells by inhibiting the binding of B7 to CTLA-4. Pharmaceutical compositions including such peptides are also provided. The invention further provides in vitro and in vivo therapeutic methods employing the peptides of the invention.

Abstract: Nucleic acids encoding novel CTLA4/CD28 ligands which costimulate T cell activation are disclosed. In one embodiment, the nucleic acid has a sequence which encodes a B lymphocyte antigen, B7-2. Preferably, the nucleic acid is a DNA molecule comprising at least a portion of a nucleotide sequence shown in FIG. 8, SEQ ID NO:1 or FIG. 14, SEQ ID NO:23. The nucleic acid sequences of the invention can be integrated into various expression vectors, which in turn direct the synthesis of the corresponding proteins or peptides in a variety of hosts, particularly eukaryotic cells, such as mammalian and insect cell culture. Also disclosed are host cells transformed to produce proteins or peptides encoded by the nucleic acid sequences of the invention and isolated proteins and peptides which comprise at least a portion of a novel B lymphocyte antigen. Proteins and peptides described herein can be administered to subjects to enhance or suppress T cell-mediated immune responses.