Evidence map›Paper›PMID 41621533›Full record

ArticleJournal of advanced research2026

Unmasking human T cell receptor germline diversity: 335 novel alleles identified in 47 Pangenome reference individuals using the gAIRR Suite.

Yu-Hsuan Yang, Chi-Yuan Yao, Mao-Jan Lin, Kuan-Ta Huang, Yu-Hui Lin, Yi-Hui Huang, I-Hsuan Chiu, Sheng-Kai Lai, Chih-Yeh Chen, Ya-Chien Yang and 4 more

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Article in Journal of advanced research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Article
  2. IMGTAntibodies (Basel, Switzerland) · 2026
    Review
  3. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Yu-Hsuan YangGraduate Institute of Medical Genomics and Proteomics, National Taiwan University, Taipei, Taiwan.
Chi-Yuan YaoDivision of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan.
Mao-Jan LinDepartment of Computer Science, Johns Hopkins University, Baltimore, MD, USA.
Kuan-Ta HuangGraduate Institute of Medical Genomics and Proteomics, National Taiwan University, Taipei, Taiwan.
Yu-Hui LinDepartment of Medical Genetics, National Taiwan University Hospital, Taipei, Taiwan.
Yi-Hui HuangDepartment of Medical Genetics, National Taiwan University Hospital, Taipei, Taiwan.
I-Hsuan ChiuDepartment of Medical Genetics, National Taiwan University Hospital, Taipei, Taiwan.
Sheng-Kai LaiDepartment of Medical Genetics, National Taiwan University Hospital, Taipei, Taiwan; Genome and Systems Biology Degree Program, Academia Sinica and National Taiwan University, Taipei, Taiwan.
Chih-Yeh ChenGraduate Institute of Medical Genomics and Proteomics, National Taiwan University, Taipei, Taiwan.
Ya-Chien YangDepartment of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan; Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University, Taipei, Taiwan.
Chia-Lang HsuGraduate Institute of Medical Genomics and Proteomics, National Taiwan University, Taipei, Taiwan; Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan.
Jacob Shujui HsuGraduate Institute of Medical Genomics and Proteomics, National Taiwan University, Taipei, Taiwan.
Chien-Yu ChenDepartment of Biomechatronics Engineering, National Taiwan University, Taipei, Taiwan.
Pei-Lung ChenGraduate Institute of Medical Genomics and Proteomics, National Taiwan University, Taipei, Taiwan; Department of Medical Genetics, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Clinical Medicine, National Taiwan University, Taipei, Taiwan; Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan. Electronic address: paylong@ntu.edu.tw.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionThe adaptive immune receptor repertoire (AIRR), also referred to as expressed AIRR (exprAIRR) for clarity, comprises V(D)J-recombined T cell receptors (TR) and immunoglobulins (IG), and is central to adaptive immunity. Accurate exprAIRR profiling depends on a comprehensive and population-representative germline gene set encoding AIRR (gAIRR). In addition to serving as the reference for AIRR-seq, gAIRR alleles themselves are increasingly recognized as contributors to immune-related phenotypes, including disease susceptibility, variable vaccine responsiveness, and adverse immune events.

objectivesCurrent germline TR references form an essential foundation, but based on scientific inference, likely represent only a portion of true human diversity. Some alleles lack flanking genomic information, and several populations remain underrepresented-constraints rooted in earlier sequencing methodologies. This study aims to substantially expand these references by resolving full-length TR alleles and their flanking regions across ancestrally diverse individuals.

methodsWe analyzed 47 high-quality, phased diploid genomes from the Human Pangenome Reference Consortium (HPRC) using the gAIRR Suite. All novel alleles were crosschecked using two orthogonal pipelines: gAIRR-annotate (assembly-based annotation) and gAIRR-seq/gAIRR-call (targeted short-read sequencing and genotyping).

resultsWe identified 335 novel TR alleles-305 TRV and 30 TRJ-representing 91.6% and 30.9% increases over IMGT records (v3.1.41; accessed 2025-04-19), respectively. Many novel alleles occurred at substantial frequencies, particularly among individuals of African ancestry. We further established a comprehensive flanking sequence database, including recombination signal sequences (RSS), and documented allele-specific variations in these regions. Functional annotation showed that several novel alleles exhibit altered coding potential, including transitions to pseudogene or open reading frames (ORFs) status.

conclusionThis study significantly expands the known landscape of human TR germline diversity and provides a rigorously validated, population-diverse resource comprising novel alleles, flanking sequences, RSS profiles, and supporting analytical tools. These improved gAIRR references are essential for accurate germline genotyping and exprAIRR profiling, and will enable improved detection of immunogenetic associations. Our findings advance precision immunogenomics and support the development of ancestry-independent yet diversity-comprehensive genotyping, vaccines, and immunotherapies.

Indexed as

Genetic VariationGenome, HumanGerm CellsReceptors, Antigen, T-CellAllelesHumansReceptors, Antigen, T-CellAdaptive immune receptor repertoire (AIRR)Expressed AIRR (exprAIRR)gAIRR SuiteGermline gene set encoding AIRR (gAIRR)Human Pangenome Reference Consortium (HPRC)ImMunoGeneTics information system (IMGT)ImmunogenomicsNovel alleleT cell receptor (TR)V(D)J recombination

Identifiers

PMID41621533
PMCPMC13669574

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.