JIPOAd
JIPOAd
PARP
ESID
  • Users Online: 313
  • Print this page
  • Email this page
ORIGINAL RESEARCH
Year : 2019  |  Volume : 2  |  Issue : 4  |  Page : 137-143

Haplotype Analysis of the T-Cell Receptor Beta (TCRB) Locus by Long-amplicon TCRB Repertoire Sequencing


1 Thermo Fisher Scientific, Austin, TX, USA
2 The University of Texas MD Anderson Cancer Center, Houston, TX, USA
3 Department of Pediatrics, Section of Immunology, Allergy, and Retrovirology, Texas Children's Hospital, Baylor College of Medicine, Houston, TX, USA
4 OmniSeq, Inc; Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA

Correspondence Address:
Timothy J Looney
Thermo Fisher Scientific, Austin, TX
USA
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/JIPO.JIPO_16_19

Get Permissions

Background: Polymorphism within the human T-cell receptor beta variable (TRBV) gene has been proposed as a risk factor for autoimmune disease and immune-related adverse events (IRAEs) during immunotherapy. Previous efforts to evaluate TRBV polymorphism by whole genome sequencing have been hampered by the repetitive nature of the T-cell receptor beta (TCRB) locus. We present a novel long-amplicon TCRB repertoire sequencing approach to enable TRBV haplotype analysis from peripheral blood. Methods: Peripheral blood leukocyte total RNA from 81 Caucasians was used for sequencing of TCRB chains via the Oncomine TCRB-LR assay (amplicon spanning CDR1, 2 and 3) and the Ion Gene Studio S5. VDJ rearrangements were annotated by comparison to the IMGT database, then mined to construct TRBV allele profiles for each individual including, where detected, novel alleles not present in the ImMunoGeneTics (IMGT) database. Finally, TRBV allele profiles were subjected to principal component analysis and k-means clustering to identify TRBV allele haplotypes. Results: Clustering analysis revealed the presence of six major sets of coincident TRBV alleles, which we term haplotype groups. Allelic diversity varied markedly across haplotype groups, with approximately one third of the cohort showing limited TRBV allelic diversity and few uncommon alleles compared to members of other groups. Analysis revealed 37 putatively novel TRBV alleles that are absent from the IMGT database. Conclusion: We demonstrate a straightforward and cost-efficient method for TRBV haplotype analysis from long-amplicon TCRB sequencing data.


[FULL TEXT] [PDF]*
Print this article     Email this article
 Next article
 Previous article
 Table of Contents

 Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
 Citation Manager
 Access Statistics
 Reader Comments
 Email Alert *
 Add to My List *
 * Requires registration (Free)
 

 Article Access Statistics
    Viewed1225    
    Printed60    
    Emailed0    
    PDF Downloaded56    
    Comments [Add]    

Recommend this journal