T-cell receptor sequencing reveals decreased diversity 18 years after early thymectomy Judith Gudmundsdottir, MD, Christina Lundqvist, MSc, Hanna Ijspeert,

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T-cell receptor sequencing reveals decreased diversity 18 years after early thymectomy Judith Gudmundsdottir, MD, Christina Lundqvist, MSc, Hanna Ijspeert, PhD, Eva van der Slik, BSc, Sólveig Óskarsdóttir, MD, PhD, Susanne Lindgren, MD, PhD, Vanja Lundberg, MD, Martin Berglund, PhD, Jenny Lingman-Framme, MD, Esbjörn Telemo, PhD, Mirjam van der Burg, PhD, Olov Ekwall, MD, PhD Journal of Allergy and Clinical Immunology Volume 140, Issue 6, Pages 1743-1746.e7 (December 2017) DOI: 10.1016/j.jaci.2017.08.002 Copyright © 2017 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 TRB chain junction characteristics and clonality. A, CD4+ junctional deletions, N- and P-nucleotides (average number, individual values with median, P value), and CDR3 length distribution (group values, mean with SEM). B, Coincidences table as described by Boyd et al3 where increased sequence recurrences indicate increased clonality, and (C) CD4+ clonality score (individual results with median and 95% CI, P value). D, Frequency of CD4+ TRB V-J chain usage (results from a single Tx individual showing distinct alterations, and a single control). Results shown as circos plots where the width of the band is proportional to the frequency. The different V regions are marked, and their combination with the different J regions shown. E-H, CD8+ results presented as above (Fig 1, A-D) in the same order (red dots and line, Tx individuals; blue dots and line, controls). CDR3, Complementarity determining region 3; ns, not significant; nt, nucleotides; Tx, thymectomized. Journal of Allergy and Clinical Immunology 2017 140, 1743-1746.e7DOI: (10.1016/j.jaci.2017.08.002) Copyright © 2017 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 Linear regression analysis showing the correlation between TRB chain clonality score and T-cell numbers. A, Clonality score versus number of total CD4+ cells. B, Clonality score versus number of total CD8+ cells. C and D, Clonality score versus number of naive CD4+ cells (Fig 2, C) (CD4+CD45RA+) and naive CD8+ cells (Fig 2, D) (CD8+CD45RA+); dotted vertical line and arrow on top of graph indicate clear distinction between Tx individuals and controls. E and F, Clonality score versus number of memory CD4+ cells (Fig 2, E) (CD4+CD45RO+) and memory CD8+ cells (Fig 2, F) (CD8+CD45RO+); double-headed arrow on top of graph indicates lack of distinction between Tx individuals and controls. Red dots, Tx individuals, blue dots, controls; individual results, linear regression with 95% CI, the Spearman correlation coefficient, r, and P value indicated on graphs. ns, Not significant; Tx, thymectomized. Journal of Allergy and Clinical Immunology 2017 140, 1743-1746.e7DOI: (10.1016/j.jaci.2017.08.002) Copyright © 2017 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E1 The ratio of naive versus memory T cells for (A) CD4+ T cells (mean for thymectomized 0.56 and controls 1.68) and (B) CD8+ T cells (mean for thymectomized 1.57 and controls 3.42) (shown as individual values, with mean and 95% CI indicated as lines and bars, and P value on graph). C, Linear regression analysis shows no correlation between clonality score and age at thymectomy. CD4+ T cells to the left, CD8+ T cells to the right (shown as individual results, linear regression with 95% CI, the Spearman correlation coefficient, r, and P value indicated on graphs). ns, Not significant. Journal of Allergy and Clinical Immunology 2017 140, 1743-1746.e7DOI: (10.1016/j.jaci.2017.08.002) Copyright © 2017 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E2 T-cell receptor amino acid usage in complementarity determining region 3 for (A) CD4+ T cells and (B) CD8+ T cells. The positively charged amino acids are indicated in red and the negatively charged in blue. Journal of Allergy and Clinical Immunology 2017 140, 1743-1746.e7DOI: (10.1016/j.jaci.2017.08.002) Copyright © 2017 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E3 CD4+ T-cell recombination chain usage for D-J, V-D, and V-J shown as circos plots. The width of the band is proportional to the frequency. Individual values for each Tx individuals (N = 11) and controls (N = 11). Tx, Thymectomized. Journal of Allergy and Clinical Immunology 2017 140, 1743-1746.e7DOI: (10.1016/j.jaci.2017.08.002) Copyright © 2017 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E4 CD8+ T-cell recombination chain usage for D-J, V-D, and V-J shown as circos plots. Individual values for each Tx individuals (N = 9) and controls (N = 11). Tx, Thymectomized. Journal of Allergy and Clinical Immunology 2017 140, 1743-1746.e7DOI: (10.1016/j.jaci.2017.08.002) Copyright © 2017 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E5 B-cell IGH chain characteristics and clonality index. A, IGH chain junctional deletions, N- and P-nucleotide insertions (average number, individual values with median, P value). B, Frequency of IGH chain amino acid usage in CDR3. The positively charged amino acids are indicated in red and the negatively charged in blue. C, CDR3 length distribution (group values, mean with SEM, nt = nucleotides). D, B-cell clonality index (individual results with median and 95% CI, P value). E, Coincidences table as described by Boyd et alE6 where increased sequence recurrences indicate increased clonality. Red dots, line, and staples, Tx individuals; blue dots, line, and staples, controls. CDR3, Complementarity determining region 3; ns, not significant; Tx, thymectomized. Journal of Allergy and Clinical Immunology 2017 140, 1743-1746.e7DOI: (10.1016/j.jaci.2017.08.002) Copyright © 2017 American Academy of Allergy, Asthma & Immunology Terms and Conditions