Abstract: The present invention provides a soluble T cell receptor (sTCR), which comprises (i) all or part of a TCR ? chain, except the transmembrane domain thereof, and (ii) all or part of a TCR ? chain, except the transmembrane domain thereof. (i) and (ii) each comprise a functional variable domain and at least a part of the constant domain of the TCR chain, and are linked by a disulphide bond between constant domain residues which is not present in native TCR.

Abstract: The present invention provides a soluble T cell receptor (sTCR), which comprises (i) all or part of a TCR $g(a) chain, except the transmembrane domain thereof, and (ii) all or part of a TCR $g(b) chain, except the transmembrane domain thereof. (i) and (ii) each comprise a functional variable domain and at least a part of the constant domain of the TCR chain, and are linked by a disulphide bond between constant domain residues which is not present in native TCR, characterized in that the sTCR recognizes a CD1-antigen complex, a bacterial superantigen or a peptide-MHC/superantigen complex.

Abstract: A single chain T cell receptor (scTCR) comprising an a segment constituted by a TCR ? chain variable region sequence fused to the N terminus of a TCR ? chain constant region extracellular sequence, a ? segment constituted by a TCR ? chain variable region fused to the N terminus of a TCR ? chain constant region extracellular sequence, and a linker sequence linking the C terminus of the ? segment to the N terminus of the ? segment, or vice versa, the constant region extracellular sequences of the ? and ? segments being linked by a disulfide bond, the length of the linker sequence and the position of the disulfide bond being such that the variable region sequences of the ? and ? segments are mutually orientated substantially as in native ?? T cell receptors. Complexes of two or more such scTCRs, and use of the scTCRs in therapy and in various screening applications are also disclosed.

Abstract: The present invention provides modified CD8 molecules whose binding to MHC is enhanced compared to wild-type CD8, wherein Ser53 of at least one CD8? chain thereof is mutated to another amino acid. It also provides nucleic acids encoding such molecules and methods of using such molecules and nucleic acids in immunosuppressive therapy, in particular as inhibitors of cytotoxic T cell responses.

Abstract: The present invention provides a soluble T cell receptor (sTCR), which comprises (i) all or part of a TCR ? chain, except the transmembrane domain thereof, and (ii) all or part of a TCR ? chain, except the transmembrane domain thereof. (i) and (ii) each comprise a functional variable domain and at least a part of the constant domain of the TCR chain, and are linked by a disulphide bond between constant domain residues which is not present in native TCR.

Abstract: The present invention provides a soluble T cell receptor (sTCR), which comprises (i) all or part of a TCR? chain, except the transmembrane domain thereof, and (ii) all or part of a TCR ? chain, except the transmembrane domain thereof. (i) and (ii) each comprise a functional variable domain and at least a part of the constant domain of the TCR chain, and are linked by a disulphide bond between constant domain residues which is not present in native TCR.

Abstract: The present invention provides a soluble T cell receptor (sTCR), which comprises (i) all for part of a TCR ? chain, except the transmembrane domain thereof, and (ii) all or part of a TCR ? chain, except the transmembrane domain thereof. (i) and (ii) each comprise a functional variable domain and at least a part of the constant domain of the TCR chain, and are linked by a disulphide bond between constant domain residues which is not present in native TCR.

Abstract: The present invention provides a soluble T cell receptor (sTCR), which comprises (i) all or part of a TCR $g(a) chain, except the transmembrane domain thereof, and (ii) all or part of a TCR $g(b) chain, except the transmembrane domain thereof. (i) and (ii) each comprise a functional variable domain and at least a part of the constant domain of the TCR chain, and are linked by a disulphide bond between constant domain residues which is not present in native TCR, characterised in that the sTCR recognises a CD1-antigen complex, a bacterial superantigen or a peptide-MHC/superantigen complex.

Abstract: A single chain T cell receptor (scTCR) comprising an a segment constituted by a TCR ? chain variable region sequence fused to the N terminus of a TCR ? chain constant region extracellular sequence, a ? segment constituted by a TCR ? chain variable region fused to the N terminus of a TCR ? chain constant region extracellular sequence, and a linker sequence linking the C terminus of the a segment to the N terminus of the ? segment, or vice versa, the constant region extracellular sequences of the ? and ? segments being linked by a disulfide bond, the length of the linker sequence and the position of the disulfide bond being such that the variable region sequences of the ? and ? segments are mutually orientated substantially as in native ?? T cell receptors. Complexes of two or more such scTCRs, and use of the scTCRs in therapy and in various screening applications are also disclosed.

Abstract: A multivalent T cell receptor (TCR) complex comprising at least two TCRs, linked by a non-peptidic polymer chain or a peptidic linker sequence. Preferably the TCR complex comprises TCR heterodimers having a non-native disulfide bond between constant domain residues, said TCRs being linked via an optionally substituted, polyalkylene glycol linker. Therapeutic agents such as cytotoxic drugs may be attached to such complexes for targeted cell delivery. Such TCR complexes may be used in the diagnosis or treatment of cancer, infectious disease, or autoimmune disease.

Abstract: A method for identifying a binding site for a ligand on a macromolecule and the configuration of the ligand when bound, said method comprising using a multiscale approach to represent the ligand as a plurality of models having different levels of detail.

Abstract: The present invention provides a soluble T cell receptor (sTCR), which comprises (i) all for part of a TCR ? chain, except the transmembrane domain thereof, and (ii) all or part of a TCR ? chain, except the transmembrane domain thereof. (i) and (ii) each comprise a functional variable domain and at least a part of the constant domain of the TCR chain, and are linked by a disulphide bond between constant domain residues which is not present in native TCR.

Abstract: The present invention provides modified CD8 molecules whose binding to MHC is enhanced compared to wild type CD8, wherein Ser53 of at least one CD8&agr; chain thereof is mutated to another amino acid. It also provides nucleic acids encoding such molecules, and to the use of such molecules and nucleic acids in immunosuppressive therapy, in particular as inhibitors of cytotoxic T cell responses.