Identification of cognate pairs of ligands and receptors

A method for treating cancer, inflammatory disease, autoimmune disease, infectious disease, or metabolic disease in a subject in need thereof comprising the steps of:

• A) providing a set of ligands comprising a plurality of ligand species, in which each ligand species is present more than one time;
• B) providing a set of receptors comprising at least one receptor species;
• C) compartmentalizing ligands and receptors to form a set of microreactors, wherein a plurality of the microreactors comprise at least one ligand species and at least one receptor species;
• D) assaying recognition between ligands and receptors within microreactors of the set of microreactors and, based on an assay readout within the microreactors, classifying microreactors of the set of microreactors as positive or negative, wherein a microreactor is classified as positive when at least one ligand and receptor in the microreactor recognize one with the other or as negative when no ligand and receptor recognize one with the other in the microreactor;
• E) identifying ligand species and receptor species contained in one or more positive microreactors;
• F) establishing a subset of positive microreactors containing a first receptor species;
• G) determining a probability that in the subset of positive microreactors containing the first receptor species, the ligand species recognized by the first receptor species corresponds to the most frequent co-compartmentalized ligand species;
• H) if the determined probability is greater than a predetermined threshold, identifying as a cognate pair the first receptor species and the most frequent co-compartmentalized ligand species,
• wherein:
• (i) an antigen is identified as being part of a TCR/antigen pair, and/or
• (ii) a T cell expressing a TCR is identified as being part of a TCR/antigen pair, and/or
• (iii) a TCR is identified as being part of a TCR/antigen pair, and/or
• (iv) an ex-vivo engineered immune cell expressing either an antigen and/or a TCR is identified as being part of a TCR/antigen pair;
• and
• administering to the subject a therapeutically effective amount of a composition comprising said identified antigen, T cell expressing a TCR, TCR, and/or said ex-vivo engineered immune cell.