Abstract: Recombinant polypeptides comprising a DR?1 domain, an antigenic peptide, and a linker sequence are disclosed. The linker sequence comprises a first glycine-serine spacer, a thrombin cleavage site and a second glycine-serine spacer. Further disclosed are pharmaceutical compositions comprising the recombinant polypeptides, methods of treating inflammatory disease using said pharmaceutical compositions, and expression constructs comprising nucleic acids that encode the recombinant polypeptides.

Abstract: The present invention provides, in particular embodiments, for modified recombinant T cell receptor (TCR) ligands (RTLs) comprising a MHC class I or MHC class II component. The modified RTLs have redesigned surface features that preclude or reduce aggregation, wherein the modified molecules retain the ability to bind Ag-peptides, target antigen-specific T cells, inhibit T cell proliferation in an Ag-specific manner and have utility to treat, inter alia, autoimmune disease and other conditions mediated by antigen-specific T cells in vivo.

Abstract: Two-domain MHC polypeptides are useful for modulating activities of antigen-specific T-cells, including for modulating pathogenic potential and effects of antigen-specific T-cells. Exemplary MHC class II-based recombinant T-cell ligands (RTLs) of the invention include covalently linked ?1 and ?1 domains, and MHC class I-based molecules that comprise covalently linked ?1 and ?2 domains. These polypeptides may also include covalently linked antigenic determinants, toxic moieties, and/or detectable labels. The disclosed polypeptides can be used to target antigen-specific T-cells, and are useful, among other things, to detect and purify antigen-specific T-cells, to induce or activate T-cells, to modulate T-cell activity, including by regulatory switching of T-cell cytokine and adhesion molecule expression, to treat conditions mediated by antigen-specific T-cells, including treatment and/or prevention of central nervous system damage relating to stroke.

Abstract: Methods are provided for the treatment of subjects with cognitive or neuropsychiatric impairment induced by substance addiction and for increasing cognitive function in a subject with substance addiction. In some embodiments, the methods include administering to the subject a therapeutically effective amount of a major histocompatibility complex (MHC) molecule including covalently linked first, second, and third domains; wherein the first domain is an MHC class II ?1 domain and the second domain is an MHC class II ?1 domain; or wherein the first domain is an MHC class I ?1 domain and the second domain is an MHC class I ?2 domain; and wherein the third domain is covalently linked to the first domain and comprises an antigen of the central or peripheral nervous system.

Abstract: The present invention provides, in particular embodiments, for modified recombinant T cell receptor (TCR) ligands (RTLs) comprising a MHC class I or MHC class II component. The modified RTLs have redesigned surface features that preclude or reduce aggregation, wherein the modified molecules retain the ability to bind Ag-peptides, target antigen-specific T cells, inhibit T cell proliferation in an Ag-specific manner and have utility to treat, inter alia, autoimmune disease and other conditions mediated by antigen-specific T cells in vivo.

Abstract: The present invention provides, in particular embodiments, for modified recombinant T cell receptor (TCR) ligands (RTLs) comprising a MHC class I or MHC class II component. The modified RTLs have redesigned surface features that preclude or reduce aggregation, wherein the modified molecules retain the ability to bind Ag-peptides, target antigen-specific T cells, inhibit T cell proliferation in an Ag-specific manner and have utility to treat, inter alia, autoimmune disease and other conditions mediated by antigen-specific T cells in vivo.

Abstract: Two-domain MHC polypeptides are useful for modulating activities of antigen-specific T-cells, including for modulating pathogenic potential and effects of antigen-specific T-cells. Exemplary MHC class II-based recombinant T-cell ligands (RTLs) of the invention include covalently linked ?1 and ?1 domains, and MHC class I-based molecules that comprise covalently linked ?1 and ?2 domains. These polypeptides may also include covalently linked antigenic determinants, toxic moieties, and/or detectable labels. The disclosed polypeptides can be used to target antigen-specific T-cells, and are useful, among other things, to detect and purify antigen-specific T-cells, to induce or activate T-cells, to modulate T-cell activity, including by regulatory switching of T-cell cytokine and adhesion molecule expression, to treat conditions mediated by antigen-specific T-cells, including treatment and/or prevention of central nervous system damage relating to stroke.

Abstract: Two-domain MHC polypeptides are useful for modulating activities of antigen-specific T-cells, including for modulating pathogenic potential and effects of antigen-specific T-cells. Exemplary MHC class II-based recombinant T-cell ligands (RTLs) of the invention include covalently linked ?1 and ?1 domains, and MHC class I-based molecules that comprise covalently linked ?1 and ?2 domains. These polypeptides may also include covalently linked antigenic determinants, toxic moieties, and/or detectable labels. The disclosed polypeptides can be used to target antigen-specific T-cells, and are useful, among other things, to detect and purify antigen-specific T-cells, to induce or activate T-cells, to modulate T-cell activity, including by regulatory switching of T-cell cytokine and adhesion molecule expression, to treat conditions mediated by antigen-specific T-cells, including treatment and/or prevention of central nervous system damage relating to stroke.

Abstract: Recombinant polypeptides comprising a DR?1 domain, an antigenic peptide, and a linker sequence are disclosed. The linker sequence comprises a first glycine-serine spacer, a thrombin cleavage site and a second glycine-serine spacer. Further disclosed are pharmaceutical compositions comprising the recombinant polypeptides, methods of treating inflammatory disease using said pharmaceutical compositions, and expression constructs comprising nucleic acids that encode the recombinant polypeptides.

Abstract: Disclosed herein are isolated major histocompatibility complex (MHC) class II ?1 domain polypeptides and methods of use. In some embodiments, the isolated polypeptide comprises or consists of an MHC class II ?1 domain polypeptide (or portion thereof) and does not include an MHC class II ?2, ?1, or ?2 domain. The disclosed MHC class II ?1 domain polypeptides are of use in treating or inhibiting disorders in a subject, such as inflammatory and/or autoimmune disorders. Also disclosed are methods of evaluating efficacy of treatment or optimizing treatment of a subject with a polypeptide including an MHC class II ?1 domain polypeptide (or portion thereof) or a polypeptide including an MHC class II ?1 domain and ?1 domain (such as a ?1?1 RTL).

Abstract: Methods are provided for the treatment of subjects with cognitive or neuropsychiatric impairment induced by substance addiction and for increasing cognitive function in a subject with substance addiction. In some embodiments, the methods include administering to the subject a therapeutically effective amount of a major histocompatibility complex (MHC) molecule including covalently linked first, second, and third domains; wherein the first domain is an MHC class II ?1 domain and the second domain is an MHC class II ?1 domain; or wherein the first domain is an MHC class I ?1 domain and the second domain is an MHC class I ?2 domain; and wherein the third domain is covalently linked to the first domain and comprises an antigen of the central or peripheral nervous system.

Abstract: Methods are provided for the treatment of subjects with cognitive or neuropsychiatric impairment induced by substance addiction and for increasing cognitive function in a subject with substance addiction. In some embodiments, the methods include administering to the subject a therapeutically effective amount of a major histocompatibility complex (MHC) molecule including covalently linked first, second, and third domains; wherein the first domain is an MHC class II ?1 domain and the second domain is an MHC class II ?1 domain; or wherein the first domain is an MHC class I ?1 domain and the second domain is an MHC class I ?2 domain; and wherein the third domain is covalently linked to the first domain and comprises an antigen of the central or peripheral nervous system.

Abstract: Two-domain MHC polypeptides are useful for modulating activities of antigen-specific T-cells, including for modulating pathogenic potential and effects of antigen-specific T-cells. Exemplary MHC class II-based recombinant T-cell ligands (RTLs) of the invention include covalently linked ?1 and ?1 domains, and MHC class I-based molecules that comprise covalently linked ?1 and ?2 domains. These polypeptides may also include covalently linked antigenic determinants, toxic moieties, and/or detectable labels. The disclosed polypeptides can be used to target antigen-specific T-cells, and are useful, among other things, to detect and purify antigen-specific T-cells, to induce or activate T-cells, to modulate T-cell activity, including by regulatory switching of T-cell cytokine and adhesion molecule expression, to treat conditions mediated by antigen-specific T-cells, including treatment and/or prevention of central nervous system damage relating to stroke.

Abstract: Methods are provided for the treatment of subjects with cognitive or neuropsychiatric impairment induced by substance addiction and for increasing cognitive function in a subject with substance addiction. In some embodiments, the methods include administering to the subject a therapeutically effective amount of a major histocompatibility complex (MHC) molecule including covalently linked first, second, and third domains; wherein the first domain is an MHC class II ?1 domain and the second domain is an MHC class II ?1 domain; or wherein the first domain is an MHC class I ?1 domain and the second domain is an MHC class I ?2 domain; and wherein the third domain is covalently linked to the first domain and comprises an antigen of the central or peripheral nervous system.

Abstract: The present invention provides, in particular embodiments, for modified recombinant T cell receptor (TCR) ligands (RTLs) comprising a MHC class I or MHC class II component. The modified RTLs have redesigned surface features that preclude or reduce aggregation, wherein the modified molecules retain the ability to bind Ag-peptides, target antigen-specific T cells, inhibit T cell proliferation in an Ag-specific manner and have utility to treat, inter alia, autoimmune disease and other conditions mediated by antigen-specific T cells in vivo.

Abstract: Two-domain MHC polypeptides are useful for modulating activities of antigen-specific T-cells, including for modulating pathogenic potential and effects of antigen-specific T-cells. Exemplary MHC class II-based recombinant T-cell ligands (RTLs) of the invention include covalently linked ?1 and ?1 domains, and MHC class I-based molecules that comprise covalently linked ?1 and ?2 domains. These polypeptides may also include covalently linked antigenic determinants, toxic moieties, and/or detectable labels. The disclosed polypeptides can be used to target antigen-specific T-cells, and are useful, among other things, to detect and purify antigen-specific T-cells, to induce or activate T-cells, to modulate T-cell activity, including by regulatory switching of T-cell cytokine and adhesion molecule expression, to treat conditions mediated by antigen-specific T-cells, including treatment and/or prevention of central nervous system damage relating to stroke.

Abstract: Disclosed herein are stable complexes including an MHC class I or MHC class II recombinant T cell receptor ligand RTL polypeptide covalently linked to an antigenic determinant by a disulfide bond. Also disclosed are methods of making such compositions and methods of use, for example to treat or inhibit a disorder, for example, an autoimmune disorder.

Abstract: The present invention provides, in particular embodiments, for modified recombinant T cell receptor (TCR) ligands (RTLs) comprising a MHC class I or MHC class II component. The modified RTLs have redesigned surface features that preclude or reduce aggregation, wherein the modified molecules retain the ability to bind Ag-peptides, target antigen-specific T cells, inhibit T cell proliferation in an Ag-specific manner and have utility to treat, inter alia, autoimmune disease and other conditions mediated by antigen-specific T cells in vivo.

Abstract: Two-domain MHC polypeptides useful for manipulation of antigen-specific T-cells are disclosed. These polypeptides include MHC class II-based molecules that comprise covalently linked ?1 and ?1 domains, and MHC class I-based molecules that comprise covalently linked ?1 and ?2 domains. These polypeptides may also include covalently linked antigenic determinants, toxic moieties, and/or detectable labels. The disclosed polypeptides can be used to target antigen-specific T-cells, and are useful, among other things, to detect and purify antigen-specific T-cells, to induce or activate T-cells, and to treat conditions mediated by antigen-specific T-cells.

Abstract: Two-domain MHC polypeptides are useful for modulating activities of antigen-specific T-cells, including for modulating pathogenic potential and effects of antigen-specific T-cells. Exemplary MHC class II-based recombinant T-cell ligands (RTLs) of the invention include covalently linked ?1 and ?1 domains, and MHC class I-based molecules that comprise covalently linked ?1 and ?2 domains. These polypeptides may also include covalently linked antigenic determinants, toxic moieties, and/or detectable labels. The disclosed polypeptides can be used to target antigen-specific T-cells, and are useful, among other things, to detect and purify antigen-specific T-cells, to induce or activate T-cells, to modulate T-cell activity, including by regulatory switching of T-cell cytokine and adhesion molecule expression, to treat conditions mediated by antigen-specific T-cells, including treatment and/or prevention of central nervous system damage relating to stroke.