Two types of human TCR differentially regulate reactivity to self and non-self antigens.

[en] Based on analyses of TCR sequences from over 1,000 individuals, we report that the TCR repertoire is composed of two ontogenically and functionally distinct types of TCRs. Their production is regulated by variations in thymic output and terminal deoxynucleotidyl transferase (TDT) activity. Neonatal TCRs derived from TDT-negative progenitors persist throughout life, are highly shared among subjects, and are reported as disease-associated. Thus, 10%-30% of most frequent cord blood TCRs are associated with common pathogens and autoantigens. TDT-dependent TCRs present distinct structural features and are less shared among subjects. TDT-dependent TCRs are produced in maximal numbers during infancy when thymic output and TDT activity reach a summit, are more abundant in subjects with AIRE mutations, and seem to play a dominant role in graft-versus-host disease. Factors decreasing thymic output (age, male sex) negatively impact TCR diversity. Males compensate for their lower repertoire diversity via hyperexpansion of selected TCR clonotypes.

Disciplines :

Biochemistry, biophysics & molecular biology

Author, co-author :

Trofimov, Assya; Institute for Research in Immunology and Cancer (IRIC), Université de Montréal, Montreal, Quebec H3C 3J7, Canada ; Department of Computer Science and Research Operations, Université de Montréal, Montreal, Quebec H3C 3J7, Canada ; Quebec Institute for Learning Algorithms (Mila), Montreal, Quebec H2S 3H1, Canada ; Currently Fred Hutchinson Cancer Center, Seattle, WA 98109, USA ; Currently Department of Physics, University of Washington, Seattle, WA 98195-1560, USA

Brouillard, Philippe; Department of Computer Science and Research Operations, Université de Montréal, Montreal, Quebec H3C 3J7, Canada ; Quebec Institute for Learning Algorithms (Mila), Montreal, Quebec H2S 3H1, Canada

Larouche, Jean-David; Institute for Research in Immunology and Cancer (IRIC), Université de Montréal, Montreal, Quebec H3C 3J7, Canada ; Department of Medicine, Université de Montréal, Montreal, Quebec H3C 3J7, Canada

Séguin, Jonathan; Institute for Research in Immunology and Cancer (IRIC), Université de Montréal, Montreal, Quebec H3C 3J7, Canada

Laverdure, Jean-Philippe; Institute for Research in Immunology and Cancer (IRIC), Université de Montréal, Montreal, Quebec H3C 3J7, Canada

Brasey, Ann; Maisonneuve-Rosemont Hospital, Montreal, Quebec H1T 2M4, Canada

Ehx, Grégory ; Université de Liège - ULiège > Département des sciences cliniques ; Institute for Research in Immunology and Cancer (IRIC), Université de Montréal, Montreal, Quebec H3C 3J7, Canada

Roy, Denis-Claude; Maisonneuve-Rosemont Hospital, Montreal, Quebec H1T 2M4, Canada

Busque, Lambert; Maisonneuve-Rosemont Hospital, Montreal, Quebec H1T 2M4, Canada

Lachance, Silvy; Department of Medicine, Université de Montréal, Montreal, Quebec H3C 3J7, Canada ; Maisonneuve-Rosemont Hospital, Montreal, Quebec H1T 2M4, Canada

Lemieux, Sébastien; Institute for Research in Immunology and Cancer (IRIC), Université de Montréal, Montreal, Quebec H3C 3J7, Canada ; Department of Computer Science and Research Operations, Université de Montréal, Montreal, Quebec H3C 3J7, Canada ; Department of Biochemistry at University of Montreal, Université de Montréal, Montreal, Quebec H3C 3J7, Canada

Perreault, Claude ; Institute for Research in Immunology and Cancer (IRIC), Université de Montréal, Montreal, Quebec H3C 3J7, Canada ; Department of Medicine, Université de Montréal, Montreal, Quebec H3C 3J7, Canada ; Maisonneuve-Rosemont Hospital, Montreal, Quebec H1T 2M4, Canada

Language :

English

Title :

Two types of human TCR differentially regulate reactivity to self and non-self antigens.

Publication date :

16 September 2022

Journal title :

iScience

eISSN :

2589-0042

Publisher :

Elsevier Inc., United States

Volume :

Issue :

Pages :

104968

Peer reviewed :

Peer Reviewed verified by ORBi

Additional URL :

https://api.elsevier.com/content/article/PII:S2589004222012408?httpAccept=text/xml

Funders :

FRQS - Fonds de Recherche du Québec - Santé [CA]
CIHR - Canadian Institutes of Health Research [CA]

Funding text :

This study was supported by grant FDN-148400 from the Canadian Institutes of Health Research (to C.P.). A.T. was supported by a studentship from the Canadian Institutes of Health Research , and J.D.L. by a studentship from the Fonds de Recherche Québec – Santé .

Available on ORBi :

since 16 January 2023

Statistics

Number of views

10 (0 by ULiège)

Number of downloads

0 (0 by ULiège)

More statistics

Scopus citations^®

Scopus citations^®
without self-citations

OpenCitations

Bibliography

Autissier, P., Soulas, C., Burdo, T.H., Williams, K.C., Evaluation of a 12-color flow cytometry panel to study lymphocyte, monocyte, and dendritic cell subsets in humans. Cytometry A 77 (2010), 410–419, 10.1002/cyto.a.20859.
Barennes, P., Quiniou, V., Shugay, M., Egorov, E.S., Davydov, A.N., Chudakov, D.M., Uddin, I., Ismail, M., Oakes, T., Chain, B., et al. Benchmarking of T cell receptor repertoire profiling methods reveals large systematic biases. Nat. Biotechnol. 39 (2020), 236–245, 10.1038/s41587-020-0656-3.
Baron, C., Somogyi, R., Greller, L.D., Rineau, V., Wilkinson, P., Cho, C.R., Cameron, M.J., Kelvin, D.J., Chagnon, P., Roy, D.-C., et al. Prediction of graft-versus-host disease in humans by donor gene-expression profiling. PLoS Med., 4, 2007, e23, 10.1371/journal.pmed.0040023.
Bentzen, A.K., Such, L., Jensen, K.K., Marquard, A.M., Jessen, L.E., Miller, N.J., Church, C.D., Lyngaa, R., Koelle, D.M., Becker, J.C., et al. T cell receptor fingerprinting enables in-depth characterization of the interactions governing recognition of peptide-MHC complexes. Nat. Biotechnol. 36 (2018), 1191–1196, 10.1038/nbt.4303.
Bernin, H., Fehling, H., Marggraff, C., Tannich, E., Lotter, H., The cytokine profile of human NKT cells and PBMCs is dependent on donor sex and stimulus. Med. Microbiol. Immunol. 205 (2016), 321–332, 10.1007/s00430-016-0449-y.
Bolotin, D.A., Poslavsky, S., Mitrophanov, I., Shugay, M., Mamedov, I.Z., Putintseva, E.V., Chudakov, D.M., MiXCR: software for comprehensive adaptive immunity profiling. Nat. Methods 12 (2015), 380–381, 10.1038/nmeth.3364.
Bonati, A., Zanelli, P., Ferrari, S., Plebani, A., Starcich, B., Savi, M., Neri, T.M., T-cell receptor beta-chain gene rearrangement and expression during human thymic ontogenesis. Blood 79 (1992), 1472–1483, 10.1182/blood.V79.6.1472.1472.
Britanova, O.V., Shugay, M., Merzlyak, E.M., Staroverov, D.B., Putintseva, E.V., Turchaninova, M.A., Mamedov, I.Z., Pogorelyy, M.V., Bolotin, D.A., Izraelson, M., et al. Dynamics of individual T cell repertoires: from cord blood to centenarians. J. Immunol. 196 (2016), 5005–5013, 10.4049/jimmunol.1600005.
Brodin, P., Davis, M.M., Human immune system variation. Nat. Rev. Immunol. 17 (2017), 21–29, 10.1038/nri.2016.125.
Buhler, S., Bettens, F., Dantin, C., Ferrari-Lacraz, S., Ansari, M., Mamez, A.-C., Masouridi-Levrat, S., Chalandon, Y., Villard, J., Genetic T-cell receptor diversity at 1 year following allogeneic hematopoietic stem cell transplantation. Leukemia 34 (2020), 1422–1432, 10.1038/s41375-019-0654-y.
Chu, N.D., Bi, H.S., Emerson, R.O., Sherwood, A.M., Birnbaum, M.E., Robins, H.S., Alm, E.J., Longitudinal immunosequencing in healthy people reveals persistent T cell receptors rich in highly public receptors. BMC Immunol., 20, 2019, 19, 10.1186/s12865-019-0300-5.
Clave, E., Araujo, I.L., Alanio, C., Patin, E., Bergstedt, J., Urrutia, A., Lopez-Lastra, S., Li, Y., Charbit, B., MacPherson, C.R., et al. Human thymopoiesis is influenced by a common genetic variant within the TCRA-TCRD locus. Sci. Transl. Med., 10, 2018, 10.1126/scitranslmed.aao2966.
Cohen, S., Roy, J., Lachance, S., Delisle, J.-S., Marinier, A., Busque, L., Roy, D.-C., Barabé, F., Ahmad, I., Bambace, N., et al. Hematopoietic stem cell transplantation using single UM171-expanded cord blood: a single-arm, phase 1-2 safety and feasibility study. Lancet Haematol. 7 (2020), e134–e145, 10.1016/S2352-3026(19)30202-9.
Davenport, M.P., Smith, N.L., Rudd, B.D., Building a T cell compartment: how immune cell development shapes function. Nat. Rev. Immunol. 20 (2020), 499–506, 10.1038/s41577-020-0332-3.
De Simone, M., Rossetti, G., Pagani, M., Single cell T cell receptor sequencing: techniques and future challenges. Front. Immunol., 9, 2018, 1638, 10.3389/fimmu.2018.01638.
Deibel, M.R. Jr., Riley, L.K., Coleman, M.S., Cibull, M.L., Fuller, S.A., Todd, E., Expression of terminal deoxynucleotidyl transferase in human thymus during ontogeny and development. J. Immunol. 131 (1983), 195–200.
DeWitt, W.S. 3rd, Smith, A., Schoch, G., Hansen, J.A., Matsen, F.A., Bradley, P., Human T cell receptor occurrence patterns encode immune history, genetic background, and receptor specificity. Elife, 7, 2018, 10.7554/eLife.38358.
Emerson, R.O., DeWitt, W.S., Vignali, M., Gravley, J., Hu, J.K., Osborne, E.J., Desmarais, C., Klinger, M., Carlson, C.S., Hansen, J.A., et al. Immunosequencing identifies signatures of cytomegalovirus exposure history and HLA-mediated effects on the T cell repertoire. Nat. Genet. 49 (2017), 659–665, 10.1038/ng.3822.
Ernst, B., Lee, D.S., Chang, J.M., Sprent, J., Surh, C.D., The peptide ligands mediating positive selection in the thymus control T cell survival and homeostatic proliferation in the periphery. Immunity 11 (1999), 173–181, 10.1016/s1074-7613(00)80092-8.
Fischer, D.S., Wu, Y., Schubert, B., Theis, F.J., Predicting antigen specificity of single T cells based on TCR CDR3 regions. Mol. Syst. Biol., 16, 2020, e9416, 10.15252/msb.20199416.
Gil, A., Kamga, L., Chirravuri-Venkata, R., Aslan, N., Clark, F., Ghersi, D., Luzuriaga, K., Selin, L.K., Epstein-barr virus epitope-major histocompatibility complex interaction combined with convergent recombination drives selection of diverse T cell receptor α and β repertoires. mBio, 11, 2020, 10.1128/mBio.00250-20.
Godfrey, D.I., Stankovic, S., Baxter, A.G., Raising the NKT cell family. Nat. Immunol. 11 (2010), 197–206, 10.1038/ni.1841.
Godfrey, D.I., Koay, H.-F., McCluskey, J., Gherardin, N.A., The biology and functional importance of MAIT cells. Nat. Immunol. 20 (2019), 1110–1128, 10.1038/s41590-019-0444-8.
Goronzy, J.J., Weyand, C.M., Mechanisms underlying T cell ageing. Nat. Rev. Immunol. 19 (2019), 573–583, 10.1038/s41577-019-0180-1.
de Greef, P.C., Oakes, T., Gerritsen, B., Ismail, M., Heather, J.M., Hermsen, R., Chain, B., de Boer, R.J., The naive T-cell receptor repertoire has an extremely broad distribution of clone sizes. Elife, 9, 2020, 10.7554/eLife.49900.
Haeryfar, S.M.M., Hickman, H.D., Irvine, K.R., Tscharke, D.C., Bennink, J.R., Yewdell, J.W., Terminal deoxynucleotidyl transferase establishes and broadens antiviral CD8+ T cell immunodominance hierarchies. J. Immunol. 181 (2008), 649–659, 10.4049/jimmunol.181.1.649.
Heikkilä, N., Sormunen, S., Mattila, J., Härkönen, T., Knip, M., Ihantola, E.-L., Kinnunen, T., Mattila, I.P., Saramäki, J., Arstila, T.P., Generation of self-reactive, shared T-cell receptor α chains in the human thymus. J. Autoimmun., 119, 2021, 102616, 10.1016/j.jaut.2021.102616.
Hogquist, K.A., Jameson, S.C., The self-obsession of T cells: how TCR signaling thresholds affect fate “decisions” and effector function. Nat. Immunol. 15 (2014), 815–823, 10.1038/ni.2938.
Jenkins, M.K., Chu, H.H., McLachlan, J.B., Moon, J.J., On the composition of the preimmune repertoire of T cells specific for Peptide-major histocompatibility complex ligands. Annu. Rev. Immunol. 28 (2010), 275–294, 10.1146/annurev-immunol-030409-101253.
Johnson, S.A., Seale, S.L., Gittelman, R.M., Rytlewski, J.A., Robins, H.S., Fields, P.A., Impact of HLA type, age and chronic viral infection on peripheral T-cell receptor sharing between unrelated individuals. PLoS One, 16, 2021, e0249484, 10.1371/journal.pone.0249484.
Kedzierska, K., Thomas, P.G., Venturi, V., Davenport, M.P., Doherty, P.C., Turner, S.J., La Gruta, N.L., Terminal deoxynucleotidyltransferase is required for the establishment of private virus-specific CD8+ TCR repertoires and facilitates optimal CTL responses. J. Immunol. 181 (2008), 2556–2562, 10.4049/jimmunol.181.4.2556.
Khosravi-Maharlooei, M., Obradovic, A., Misra, A., Motwani, K., Holzl, M., Seay, H.R., DeWolf, S., Nauman, G., Danzl, N., Li, H., et al. Crossreactive public TCR sequences undergo positive selection in the human thymic repertoire. J. Clin. Invest. 129 (2019), 2446–2462, 10.1172/JCI124358.
Kim, H.T., Zhang, M.-J., Woolfrey, A.E., St Martin, A., Chen, J., Saber, W., Perales, M.-A., Armand, P., Eapen, M., Donor and recipient sex in allogeneic stem cell transplantation: what really matters. Haematologica 101 (2016), 1260–1266, 10.3324/haematol.2016.147645.
Krishna, C., Chowell, D., Gönen, M., Elhanati, Y., Chan, T.A., Genetic and environmental determinants of human TCR repertoire diversity. Immun. Ageing, 17, 2020, 26, 10.1186/s12979-020-00195-9.
Li, B., Li, T., Wang, B., Dou, R., Zhang, J., Liu, J.S., Liu, X.S., Ultrasensitive detection of TCR hypervariable-region sequences in solid-tissue RNA-seq data. Nat. Genet. 49 (2017), 482–483, 10.1038/ng.3820.
Liston, A., Lesage, S., Wilson, J., Peltonen, L., Goodnow, C.C., Aire regulates negative selection of organ-specific T cells. Nat. Immunol. 4 (2003), 350–354, 10.1038/ni906.
Liston, A., Carr, E.J., Linterman, M.A., Shaping variation in the human immune system. Trends Immunol. 37 (2016), 637–646, 10.1016/j.it.2016.08.002.
Liston, A., Humblet-Baron, S., Duffy, D., Goris, A., Human immune diversity: from evolution to modernity. Nat. Immunol. 22 (2021), 1479–1489, 10.1038/s41590-021-01058-1.
Lu, J., Van Laethem, F., Bhattacharya, A., Craveiro, M., Saba, I., Chu, J., Love, N.C., Tikhonova, A., Radaev, S., Sun, X., et al. Molecular constraints on CDR3 for thymic selection of MHC-restricted TCRs from a random pre-selection repertoire. Nat. Commun., 10, 2019, 1019, 10.1038/s41467-019-08906-7.
Lythe, G., Callard, R.E., Hoare, R.L., Molina-París, C., How many TCR clonotypes does a body maintain?. J. Theor. Biol. 389 (2016), 214–224, 10.1016/j.jtbi.2015.10.016.
Madi, A., Shifrut, E., Reich-Zeliger, S., Gal, H., Best, K., Ndifon, W., Chain, B., Cohen, I.R., Friedman, N., T-cell receptor repertoires share a restricted set of public and abundant CDR3 sequences that are associated with self-related immunity. Genome Res. 24 (2014), 1603–1612, 10.1101/gr.170753.113.
Marcou, Q., Mora, T., Walczak, A.M., High-throughput immune repertoire analysis with IGoR. Nat. Commun., 9, 2018, 561, 10.1038/s41467-018-02832-w.
Martin, P.J., Increased disparity for minor histocompatibility antigens as a potential cause of increased GVHD risk in marrow transplantation from unrelated donors compared with related donors. Bone Marrow Transplant. 8 (1991), 217–223.
Martin, P.J., Levine, D.M., Storer, B.E., Warren, E.H., Zheng, X., Nelson, S.C., Smith, A.G., Mortensen, B.K., Hansen, J.A., Genome-wide minor histocompatibility matching as related to the risk of graft-versus-host disease. Blood 129 (2017), 791–798, 10.1182/blood-2016-09-737700.
Mayer, A., Balasubramanian, V., Walczak, A.M., Mora, T., How a well-adapting immune system remembers. Proc. Natl. Acad. Sci. USA 116 (2019), 8815–8823, 10.1073/pnas.1812810116.
Mittelbrunn, M., Kroemer, G., Hallmarks of T cell aging. Nat. Immunol. 22 (2021), 687–698, 10.1038/s41590-021-00927-z.
Murray, J.M., Kaufmann, G.R., Hodgkin, P.D., Lewin, S.R., Kelleher, A.D., Davenport, M.P., Zaunders, J.J., Naive T cells are maintained by thymic output in early ages but by proliferation without phenotypic change after age twenty. Immunol. Cell Biol. 81 (2003), 487–495, 10.1046/j.1440-1711.2003.01191.x.
Natarajan, A., Krogsgaard, M., The myriad targets of a T cell. Nat. Biotechnol. 36 (2018), 1152–1154, 10.1038/nbt.4309.
Ni, X., Song, Q., Cassady, K., Deng, R., Jin, H., Zhang, M., Dong, H., Forman, S., Martin, P.J., Chen, Y.-Z., et al. PD-L1 interacts with CD80 to regulate graft-versus-leukemia activity of donor CD8+ T cells. J. Clin. Invest. 127 (2017), 1960–1977, 10.1172/JCI91138.
Pahwa, R.N., Modak, M.J., McMorrow, T., Pahwa, S., Fernandes, G., Good, R.A., Terminal deoxynucleotidyl transferase (TdT) enzyme in thymus and bone marrow. I. Age-associated decline of TdT in humans and mice. Cell. Immunol. 58 (1981), 39–48, 10.1016/0008-8749(81)90147-7.
Palmer, S., Albergante, L., Blackburn, C.C., Newman, T.J., Thymic involution and rising disease incidence with age. Proc. Natl. Acad. Sci. USA 115 (2018), 1883–1888, 10.1073/pnas.1714478115.
Pauken, K.E., Lagattuta, K.A., Lu, B.Y., Lucca, L.E., Daud, A.I., Hafler, D.A., Kluger, H.M., Raychaudhuri, S., Sharpe, A.H., TCR-sequencing in cancer and autoimmunity: barcodes and beyond. Trends Immunol. 43 (2022), 180–194, 10.1016/j.it.2022.01.002.
Pogorelyy, M.V., Elhanati, Y., Marcou, Q., Sycheva, A.L., Komech, E.A., Nazarov, V.I., Britanova, O.V., Chudakov, D.M., Mamedov, I.Z., Lebedev, Y.B., et al. Persisting fetal clonotypes influence the structure and overlap of adult human T cell receptor repertoires. PLoS Comput. Biol., 13, 2017, e1005572, 10.1371/journal.pcbi.1005572.
Pogorelyy, M.V., Minervina, A.A., Touzel, M.P., Sycheva, A.L., Komech, E.A., Kovalenko, E.I., Karganova, G.G., Egorov, E.S., Komkov, A.Y., Chudakov, D.M., et al. Precise tracking of vaccine-responding T cell clones reveals convergent and personalized response in identical twins. Proc. Natl. Acad. Sci. USA 115 (2018), 12704–12709, 10.1073/pnas.1809642115.
Quigley, M.F., Greenaway, H.Y., Venturi, V., Lindsay, R., Quinn, K.M., Seder, R.A., Douek, D.C., Davenport, M.P., Price, D.A., Convergent recombination shapes the clonotypic landscape of the naive T-cell repertoire. Proc. Natl. Acad. Sci. USA 107 (2010), 19414–19419, 10.1073/pnas.1010586107.
Rudd, B.D., Neonatal T cells: a reinterpretation. Annu. Rev. Immunol. 38 (2020), 229–247, 10.1146/annurev-immunol-091319-083608.
Sethna, Z., Elhanati, Y., Callan, C.G., Walczak, A.M., Mora, T., OLGA: fast computation of generation probabilities of B- and T-cell receptor amino acid sequences and motifs. Bioinformatics 35 (2019), 2974–2981, 10.1093/bioinformatics/btz035.
Shannon, C.E., A mathematical theory of communication. Bell Syst. Tech. J. 27 (1948), 623–656, 10.1002/j.1538-7305.1948.tb00917.x.
Simpson, E.H., Measurement of diversity. Nature, 163, 1949, 688, 10.1038/163688a0.
Sng, J., Ayoglu, B., Chen, J.W., Schickel, J.-N., Ferre, E.M.N., Glauzy, S., Romberg, N., Hoenig, M., Cunningham-Rundles, C., Utz, P.J., et al. AIRE expression controls the peripheral selection of autoreactive B cells. Sci. Immunol., 4, 2019, 10.1126/sciimmunol.aav6778.
Socié, G., Blazar, B.R., Acute graft-versus-host disease: from the bench to the bedside. Blood 114 (2009), 4327–4336, 10.1182/blood-2009-06-204669.
Sood, A., Lebel, M.-È., Dong, M., Fournier, M., Vobecky, S.J., Haddad, É., Delisle, J.-S., Mandl, J.N., Vrisekoop, N., Melichar, H.J., CD5 levels define functionally heterogeneous populations of naïve human CD4+ T cells. Eur. J. Immunol. 51 (2021), 1365–1376, 10.1002/eji.202048788.
Soto, C., Bombardi, R.G., Kozhevnikov, M., Sinkovits, R.S., Chen, E.C., Branchizio, A., Kose, N., Day, S.B., Pilkinton, M., Gujral, M., et al. High frequency of shared clonotypes in human T cell receptor repertoires. Cell Rep., 32, 2020, 107882, 10.1016/j.celrep.2020.107882.
Springer, I., Besser, H., Tickotsky-Moskovitz, N., Dvorkin, S., Louzoun, Y., Prediction of specific TCR-peptide binding from large dictionaries of TCR-peptide pairs. Front. Immunol., 11, 2020, 1803, 10.3389/fimmu.2020.01803.
Springer, I., Tickotsky, N., Louzoun, Y., Contribution of T Cell receptor alpha and beta CDR3, MHC typing, V and J genes to peptide binding prediction. Front. Immunol., 12, 2021, 664514, 10.3389/fimmu.2021.664514.
Tanno, H., Gould, T.M., McDaniel, J.R., Cao, W., Tanno, Y., Durrett, R.E., Park, D., Cate, S.J., Hildebrand, W.H., Dekker, C.L., et al. Determinants governing T cell receptor α/β-chain pairing in repertoire formation of identical twins. Proc. Natl. Acad. Sci. USA 117 (2020), 532–540, 10.1073/pnas.1915008117.
Thome, J.J.C., Grinshpun, B., Kumar, B.V., Kubota, M., Ohmura, Y., Lerner, H., Sempowski, G.D., Shen, Y., Farber, D.L., Longterm maintenance of human naive T cells through in situ homeostasis in lymphoid tissue sites. Sci. Immunol., 1, 2016, 10.1126/sciimmunol.aah6506.
Tickotsky, N., Sagiv, T., Prilusky, J., Shifrut, E., Friedman, N., McPAS-TCR: a manually curated catalogue of pathology-associated T cell receptor sequences. Bioinformatics 33 (2017), 2924–2929, 10.1093/bioinformatics/btx286.
Venturi, V., Chin, H.Y., Asher, T.E., Ladell, K., Scheinberg, P., Bornstein, E., van Bockel, D., Kelleher, A.D., Douek, D.C., Price, D.A., Davenport, M.P., TCR beta-chain sharing in human CD8+ T cell responses to cytomegalovirus and EBV. J. Immunol. 181 (2008), 7853–7862, 10.4049/jimmunol.181.11.7853.
Vincent, K., Roy, D.-C., Perreault, C., Next-generation leukemia immunotherapy. Blood 118 (2011), 2951–2959, 10.1182/blood-2011-04-350868.
Vrisekoop, N., Monteiro, J.P., Mandl, J.N., Germain, R.N., Revisiting thymic positive selection and the mature T cell repertoire for antigen. Immunity 41 (2014), 181–190, 10.1016/j.immuni.2014.07.007.
Warren, E.H., Zhang, X.C., Li, S., Fan, W., Storer, B.E., Chien, J.W., Boeckh, M.J., Zhao, L.P., Martin, P.J., Hansen, J.A., Effect of MHC and non-MHC donor/recipient genetic disparity on the outcome of allogeneic HCT. Blood 120 (2012), 2796–2806, 10.1182/blood-2012-04-347286.
Wooldridge, L., Ekeruche-Makinde, J., van den Berg, H.A., Skowera, A., Miles, J.J., Tan, M.P., Dolton, G., Clement, M., Llewellyn-Lacey, S., Price, D.A., et al. A single autoimmune T cell receptor recognizes more than a million different peptides. J. Biol. Chem. 287 (2012), 1168–1177, 10.1074/jbc.M111.289488.
Ye, J., Ma, N., Madden, T. L, Ostell, J. M, IgBLAST: An immunoglobulin variable domain sequence analysis tool. Nucleic Acids Res. 41:Web Server Issue (2013), 34–40, 10.1093/nar/gkt382.
Yew, P.Y., Alachkar, H., Yamaguchi, R., Kiyotani, K., Fang, H., Yap, K.L., Liu, H.T., Wickrema, A., Artz, A., van Besien, K., et al. Quantitative characterization of T-cell repertoire in allogeneic hematopoietic stem cell transplant recipients. Bone Marrow Transplant. 50 (2015), 1227–1234, 10.1038/bmt.2015.133.
Yousefzadeh, M.J., Flores, R.R., Zhu, Y., Schmiechen, Z.C., Brooks, R.W., Trussoni, C.E., Cui, Y., Angelini, L., Lee, K.-A., McGowan, S.J., et al. An aged immune system drives senescence and ageing of solid organs. Nature 594 (2021), 100–105, 10.1038/s41586-021-03547-7.
Zhang, S.-Q., Ma, K.-Y., Schonnesen, A.A., Zhang, M., He, C., Sun, E., Williams, C.M., Jia, W., Jiang, N., High-throughput determination of the antigen specificities of T cell receptors in single cells. Nat. Biotechnol. 36 (2018), 1156–1159, 10.1038/nbt.4282.