Viral stealth technology to prevent T cell-mediated rejection of xenografts
AssigneeBoard of Trustees of the University of Arkansas
InventorMark D. Crew
Life of this patent
Estimating the term…
Loading patent…
AssigneeBoard of Trustees of the University of Arkansas
InventorMark D. Crew
Estimating the term…
The invention comprises exploiting viral stealth mechanisms to eliminate pig MHC class I cell-surface expression. PK(15) (pig kidney) cells stably transfected with the Herpes Simplex Virus (HSV) ICP47 gene [PK(15)-ICP47 cells] exhibited a dramatic reduction of MHC class I cell-surface expression when compared to untransfected PK(15) cells. To test the effect of down-regulation of porcine MHC class I on human cellular immune responses, a human CD8+ enriched T cell line (anti-PK15 T cells) with reactivity towards PK(15) cells was derived by repeated stimulation of human T cells with PK(15) cells stably transfected with the co-stimulatory molecule B7.1 [PK(15)-B7.1 cells]. Anti-PK15 T cells efficiently lysed PK(15) cells but not PK(15)-ICP47 (class I negative) cells. Consistent with effector function, anti-PK15 T cells showed a robust proliferative response to PK(15)-B7.1 cells but did not proliferate at all to PK(15)-B7.1 cells which also expressed HSV ICP47.
An isolated or synthetic protein comprising an amino acid sequence selected from the group consisting of:
An isolated nucleic acid molecule having a nucleotide sequence selected from the group consisting of:
A method of generating xenoreactive human T cells, comprising introducing into a nonhuman cell, a sequence selected from the group consisting of:
A method of inhibiting recognition of a nonhuman cell after xenotransplantation, comprising introducing into said nonhuman cell, a sequence selected from the group consisting of:
A method of conferring resistance of a nonhuman cell after xenotransplantation, comprising introducing into said nonhuman cell, a sequence selected from the group consisting of:
A method of inhibiting human T cell proliferative response to a nonhuman cell, after xenotransplantation, comprising introducing into said nonhuman cell, a sequence selected from the group consisting of:
Dependencies are inferred from the claim text.