A method for monitoring rejection of a solid organ transplant in a recipient subject comprising: (a) generating a clonotype profile from a first sample and generating a clonotype profile from a second sample, wherein each clonotype profile is a profile of recombined DNA sequences in T-cells and/or B-cells generated by next generation nucleic acid sequencing of individual, spatially isolated molecules from the sample, and wherein i. the first sample comprises activated lymphocytes, wherein the activated lymphocytes are isolated from a sample comprising irradiated lymphocytes of a donor subject mixed with peripheral blood mononuclear cells of the recipient subject, and/or wherein the first sample comprises replicated cells, wherein the replicated cells are obtained by mixing irradiated lymphocytes of a donor subject with peripheral blood mononuclear cells of the recipient subject and replicating the cells in vitro; and ii. the second sample comprises pre-activation peripheral blood mononuclear cells of the recipient subject; and (b) determining one or more correlating clonotypes in the recipient subject based on comparing the clonotype profile of the first sample with the clonotype profile of the second sample, wherein the one or more correlating clonotypes are transplant rejection relevant clonotypes; and (c) monitoring rejection of the solid organ transplant by monitoring the levels of the one or more correlating clonotypes in blood obtained from the recipient. (a) generating a clonotype profile from a first sample and generating a clonotype profile from a second sample, wherein each clonotype profile is a profile of recombined DNA sequences in T-cells and/or B-cells generated by next generation nucleic acid sequencing of individual, spatially isolated molecules from the sample, and wherein i. the first sample comprises activated lymphocytes, wherein the activated lymphocytes are isolated from a sample comprising irradiated lymphocytes of a donor subject mixed with peripheral blood mononuclear cells of the recipient subject, and/or wherein the first sample comprises replicated cells, wherein the replicated cells are obtained by mixing irradiated lymphocytes of a donor subject with peripheral blood mononuclear cells of the recipient subject and replicating the cells in vitro; and ii. the second sample comprises pre-activation peripheral blood mononuclear cells of the recipient subject; and i. the first sample comprises activated lymphocytes, wherein the activated lymphocytes are isolated from a sample comprising irradiated lymphocytes of a donor subject mixed with peripheral blood mononuclear cells of the recipient subject, and/or wherein the first sample comprises replicated cells, wherein the replicated cells are obtained by mixing irradiated lymphocytes of a donor subject with peripheral blood mononuclear cells of the recipient subject and replicating the cells in vitro; and ii. the second sample comprises pre-activation peripheral blood mononuclear cells of the recipient subject; and (b) determining one or more correlating clonotypes in the recipient subject based on comparing the clonotype profile of the first sample with the clonotype profile of the second sample, wherein the one or more correlating clonotypes are transplant rejection relevant clonotypes; and (c) monitoring rejection of the solid organ transplant by monitoring the levels of the one or more correlating clonotypes in blood obtained from the recipient.