T cell receptor beta germline variability is revealed by inference from repertoire data

• DOI: 10.1186/s13073-021-01008-4
• Publication Date: 2022-01-07T00:04:17Z
• Authors: Aviv Omer; Ayelet Peres; Oscar L Rodriguez; Corey T Watson; William Lees; Pazit Polak; Andrew M Collins; Gur Yaari
• Keywords: Immune receptor

Abstract Background T and B cell receptor (TCR, BCR) repertoires constitute the foundation of adaptive immunity. Adaptive immune repertoire sequencing (AIRR-seq) is a common approach to study system dynamics. Understanding genetic factors influencing composition dynamics these major scientific clinical importance. The chromosomal loci encoding for variable regions TCRs BCRs are challenging decipher due repetitive elements undocumented structural variants. Methods To confront this challenge, AIRR-seq-based methods have recently been developed cells, enabling genotype haplotype inference discovery alleles. However, relies on complete coverage receptors’ regions, whereas most studies sequence small fraction that region. Here, we adapted pipeline alleles, genotype, full partial AIRR-seq TCR data sets. also deals with gene assignment ambiguities, which especially important in analysis sets sequences. Results From sets, identified 39 polymorphisms Beta V (TRBV) 31 5 ′ UTR A subset inferences was observed using independent genomic approaches. We found single nucleotide polymorphism differentiating between two documented D2 (TRBD2) alleles strongly associated dramatic changes expressed repertoire. Conclusions reveal rich picture germline variability demonstrate how dramatically affects whole Our findings provide basis annotation future basic studies.