Compositions and methods for modulating lymphocyte activity
The invention derives from the identification of HVEM as the native ligand for BTLA. The invention provides compositions and methods for modulating BTLA-HVEM interactions and BTLA and HVEM activity, which are useful for modulating immune responses. Agonists and antagonists of the BTLA-HVEM interaction are provided, and methods of treating a variety of conditions through the modulation of immune responses are provided.
1. An antibody that specifically binds to a protein comprising the amino acid sequence set forth in SEQ ID NO:2, wherein the antibody is capable of reducing or eliminating phosphorylation of intracellular domain tyrosine residues of said protein or binding of said protein to SHP-2, wherein the antibody is capable of reducing binding of said protein to an HVEM protein.
2. An anti-BTLA antibody capable of reducing or eliminating phosphorylation of BTLA intracellular domain tyrosine residues or binding of BTLA to SHP-2, wherein the antibody is capable of reducing binding of the protein comprising the amino acid sequence set forth in SEQ ID NO: 2 to an HVEM protein.
3. An antibody that specifically binds to an epitope in the Ig domain of a BTLA protein, the BTLA protein comprising the amino acid sequence set forth in SEQ ID NO:2, wherein the antibody is capable of reducing or eliminating phosphorylation of BTLA intracellular domain tyrosine residues or binding of BTLA to SHP-2, wherein the antibody is capable of reducing binding of the protein comprising the amino acid sequence set forth in SEQ ID NO: 2 to an HVEM protein.
4. An antibody that specifically binds to an epitope of a human BTLA protein, the epitope comprising one or more residues selected from the group consisting of V36, Q37, L38, L49, E57, C79, K93, and S96 of SEQ ID NO:2, wherein the antibody is capable of reducing or eliminating phosphorylation of BTLA intracellular domain tyrosine residues or binding of BTLA to SHP-2, and wherein the antibody is capable of reducing binding of the protein comprising the amino acid sequence set forth in SEQ ID NO: 2 said to an HVEM protein.