Methods and compositions for noninvasive detection of organ transplant rejection

1 . A method of detecting a T cell cytotoxicity driven immune condition and/or the likelihood thereof in a subject, the method comprising:

i) administering a nanosensor to the subject, said nanosensor comprising:

a) a scaffold;

b) a peptide substrate coupled to the scaffold, wherein the peptide substrate is capable of being cleaved by Granzyme B; and

c) a detectable reporter coupled to the scaffold by the peptide substrate, wherein in vivo cleavage of said peptide substrate releases said detectable reporter from the scaffold;

ii) detecting a level of said detectable reporter in a blood or urine sample collected from the subject; wherein the presence of detectable reporter indicates the subject has or is likely to have a T cell cytotoxicity driven immune condition; and

iii) treating the subject for a T cell cytotoxicity driven immune condition when the detectable reporter is detected.

2 . The method of claim 1 , wherein said nanosensor comprises said detectable reporter selected from a group consisting of a fluorophore, a luminescent reporter, a ligand encoded reporter, a mass spectrometry tag, a contrast agent for imaging, a PET-detectable domain, and a nucleic acid tag.

3 . The method of claim 2 , wherein said detectable reporter further comprises a quencher.

4 . The method of claim 1 , wherein said peptide substrate comprises an amino acid sequence selected from the group consisting of SEQ ID Nos: 2-136.

5 . The method of claim 1 , wherein ii) further comprises comparing said level of said detectable reporter to a reference level of detectable reporter in a subject without a T cell cytotoxicity driven immune condition.

6 . The method of claim 1 , wherein i) comprises intravenously administering the nanosensor to the subject.

7 . The method of claim 1 , wherein the scaffold comprises a protein scaffold, a polymer scaffold, a DNA scaffold, a sugar scaffold, or a nanoparticle.