Profiling T Cell Receptor and Immunoglobulin Repertoires Through RNA Sequencing to Understand Host Response to Trypanosoma cruzi Infection.

The adaptive immune response is integral to controlling infections. Both T-cell receptors (TCRs) and immunoglobulin G (IgG) recognize antigens via hypervariable regions in their binding sites, referred to as complementarity determining regions (CDRs), of which CDR3 is one of the best characterized. CDR3 sequence diversity is generated by rearrangement of the respective TCR and IgG variable (V), joining (J), and diversity (D) gene segments during cell maturation, which can produce a highly diverse repertoire of TCR or IgG clonotypes. The diversity of clonotypes produced, as well as the expansion of some and/or their replacement by others, illustrates host responses to infection and its efficacy. It may also reflect changes induced by vaccination or treatment, guiding their optimization. Here, we present a method for the analysis of the TCR and IgG immune repertoire from bulk RNA-sequencing data of peripheral blood mononuclear cells (PBMCs) from Rhesus macaques, with a focus on CDR3 sequences in the context of Trypanosoma cruzi infection, a protozoan parasite causing chronic disease.