» Articles » PMID: 23995877

IMGT/HighV QUEST Paradigm for T Cell Receptor IMGT Clonotype Diversity and Next Generation Repertoire Immunoprofiling

Abstract

T cell repertoire diversity and clonotype follow-up in vaccination, cancer, infectious and immune diseases represent a major challenge owing to the enormous complexity of the data generated. Here we describe a next generation methodology, which combines 5'RACE PCR, 454 sequencing and, for analysis, IMGT, the international ImMunoGeneTics information system (IMGT), IMGT/HighV-QUEST web portal and IMGT-ONTOLOGY concepts. The approach is validated in a human case study of T cell receptor beta (TRB) repertoire, by chronologically tracking the effects of influenza vaccination on conventional and regulatory T cell subpopulations. The IMGT/HighV-QUEST paradigm defines standards for genotype/haplotype analysis and characterization of IMGT clonotypes for clonal diversity and expression and achieves a degree of resolution for next generation sequencing verifiable by the user at the sequence level, while providing a normalized reference immunoprofile for human TRB.

Citing Articles

Contrastive Learning Enables Epitope Overlap Predictions for Targeted Antibody Discovery.

Holt C, Janke A, Amlashi P, Jamieson P, Marinov T, Georgiev I bioRxiv. 2025; .

PMID: 40060439 PMC: 11888244. DOI: 10.1101/2025.02.25.640114.


Complement C3d enables cell-mediated immunity capable of distinguishing spontaneously transformed from nontransformed cells.

Platt J, Zhao C, Chicca J, Pianko M, Han J, The S Proc Natl Acad Sci U S A. 2024; 121(52):e2405824121.

PMID: 39693340 PMC: 11670236. DOI: 10.1073/pnas.2405824121.


Systematic characterization of immunoglobulin loci and deep sequencing of the expressed repertoire in the Atlantic cod (Gadus morhua).

Gyorkei A, Johansen F, Qiao S BMC Genomics. 2024; 25(1):663.

PMID: 38961347 PMC: 11223323. DOI: 10.1186/s12864-024-10571-0.


Immunoglobulin and T cell receptor repertoire changes induced by a prototype vaccine against Chagas disease in naïve rhesus macaques.

Dumonteil E, Tu W, Desale H, Goff K, Marx P, Ortega-Lopez J J Biomed Sci. 2024; 31(1):58.

PMID: 38824576 PMC: 11143712. DOI: 10.1186/s12929-024-01050-5.


Antibodies from dengue patients with prior exposure to Japanese encephalitis virus are broadly neutralizing against Zika virus.

Salem G, Galula J, Wu S, Liu J, Chen Y, Wang W Commun Biol. 2024; 7(1):15.

PMID: 38267569 PMC: 10808242. DOI: 10.1038/s42003-023-05661-w.


References
1.
Fontenot J, Rudensky A . A well adapted regulatory contrivance: regulatory T cell development and the forkhead family transcription factor Foxp3. Nat Immunol. 2005; 6(4):331-7. DOI: 10.1038/ni1179. View

2.
Miles J, Borg N, Brennan R, Tynan F, Kjer-Nielsen L, Silins S . TCR alpha genes direct MHC restriction in the potent human T cell response to a class I-bound viral epitope. J Immunol. 2006; 177(10):6804-14. DOI: 10.4049/jimmunol.177.10.6804. View

3.
Menezes J, van den Elzen P, Thornes J, Huffman D, Droin N, Maverakis E . A public T cell clonotype within a heterogeneous autoreactive repertoire is dominant in driving EAE. J Clin Invest. 2007; 117(8):2176-85. PMC: 1906731. DOI: 10.1172/JCI28277. View

4.
Lefranc M, Pommie C, Ruiz M, Giudicelli V, Foulquier E, Truong L . IMGT unique numbering for immunoglobulin and T cell receptor variable domains and Ig superfamily V-like domains. Dev Comp Immunol. 2002; 27(1):55-77. DOI: 10.1016/s0145-305x(02)00039-3. View

5.
Wang C, Sanders C, Yang Q, Schroeder Jr H, Wang E, Babrzadeh F . High throughput sequencing reveals a complex pattern of dynamic interrelationships among human T cell subsets. Proc Natl Acad Sci U S A. 2010; 107(4):1518-23. PMC: 2824416. DOI: 10.1073/pnas.0913939107. View