Development of genomic resources and assays for immune repertoire profiling in Syrian hamsters

The Syrian hamster (Mesocricetus auratus) is an important model for human infectious diseases, particularly those that infect the respiratory tract, due to having similar disease progression and immune responses as humans. However, immune repertoire studies are extremely limited due to incomplete genomic characterization of hamster B and T cell receptor loci. To begin to develop hamster immunoglobulin (IG) and T cell receptor (TR) reference resources, we first performed long-read transcriptome sequencing of six tissue types. We obtained 43,090 full-length IG/TR transcripts which were used to construct a reference set of 22 IG/TR constant (C) regions. The completeness and accuracy of this C region reference sequence set were assessed using an independent hamster single cell transcriptome sequencing dataset. C region allelic variations were only observed in two subclasses, IGHE and TRBC1. IGHE produced a synonymous variant, whereas TRBC1 resulted in a non-synonymous variant (S71G) in the DE loop, which was predicted with minimal impact on the protein structure. Furthermore, we designed and experimentally validated a set of species-specific primers that target IG/TR C regions for immune repertoire profiling analysis. These improved resources and assays will enable future studies to comprehensively capture hamster immune repertoire diversity.