Spatial transcriptomics for antigen-receptors

A method for determining the presence of an immune cell clonotype at a location in a biological sample, the method comprising:

• (a) contacting a biological sample with an array comprising a plurality of capture probes, wherein a capture probe of the plurality of capture probes comprises (i) a spatial barcode and (ii) a capture domain that hybridizes to a poly(A) sequence of a nucleic acid encoding an immune cell receptor of the immune cell clonotype;
• (b) hybridizing the capture domain to the nucleic acid encoding the immune cell receptor of the immune cell clonotype;
• (c) extending the capture probe using the nucleic acid encoding the immune cell receptor as a template to generate an extended capture probe comprising a sequence encoding a CDR3, or a complement thereof, of the immune cell receptor of the immune cell clonotype;
• (d) hybridizing one or more probes to the extended capture probe, or a complement thereof, in a portion encoding a constant region of the immune cell receptor of the immune cell clonotype, wherein the one or more probes comprises a binding moiety capable of binding a capture moiety;
• (e) enriching the extended capture probe or the complement thereof via an interaction between the binding moiety in the one or more probes and the capture moiety;
• and
• (f) determining (i) the sequence of the spatial barcode or a complement thereof, and (ii) all or a portion of the sequence of the nucleic acid encoding the immune cell receptor of the immune cell clonotype or a complement thereof, and using the determined sequences of (i) and (ii) to determine the presence of the immune cell clonotype at a location in the biological sample.