Supplementary Figure 1. (A) V-gene usage of T cells in the cerebrospinal fluid (CSF) and blood from patients

with MS and controls with other inflammatory neurological diseases (OIND). There were no significant

differences between these T cell populations for any V-gene. The V-genes 3-2, 5-3, 5-7, 6-5, 6-6, 6-7, 6-8, 6-9,

7-1, 7-4, 7-5, 10-2, 11-1, 12-1, 12-2, 17, 21-1, 25-1 had relative frequencies below 0.1% and were omitted from

the figure. (B) J-gene usage of T cells in the cerebrospinal fluid (CSF) and blood from patients with MS and

controls with other inflammatory neurological diseases (OIND). No significant differences were found for any J-

gene. Comparisons were done using Friedman's 2-way ANOVA by ranks and Mann-Whitney U tests, and results

are presented as mean ± 95% confidence interval.

V2-1V3-1V4-1V4-2

V4-2/V4-3V5-1V5-4V5-5V5-6V5-8V6-1

V6-2/V6-3V6-4V7-2V7-3V7-6V7-7V7-8V7-9V9-1V10-1V10-3

V11-02

V11-03

V12-3/V12-4V12-5V13-1V14-1V15-1V16-1V18-1V19-1V20-1V23-1V24-1V27-1V28-1V29-1V30-1

0

5

10

15

20

Rela

tive

frequ

ency

(%)

J1-1J1-2J1-3J1-4J1-5J1-6J2-1J2-2J2-3J2-4J2-5J2-6J2-7

0

5

10

15

20

25

Rela

tive

frequ

ency

(%)

MS CSFOIND CSFMS bloodOIND blood

A

B

HLA-B8/B35-restricted public TCRβ sequences*

HLA-A2-restricted public TCRβ sequences*

HLA-A2 + HLA-A2 –

HLA-B8/B35 + HLA-B8/B35 –

1

0.1

0.01

0

MS-2MS-3

MS-5MS-7

MS-9MS-10

OIND-3

OIND-4

OIND-5OIND-7

OIND-11 MS-1MS-4

MS-6MS-8

OIND-1OIND-2

OIND-6

OIND-8

OIND-9

OIND-10

MS-1MS-2

MS-3MS-4

MS-5MS-6

MS-7MS-9

MS-10

OIND-2OIND-4

OIND-7

OIND-8

OIND-10

AFr

eque

ncy

(%)

B

1

0.1

0.01

0

Freq

uenc

y (%

)

MS-8

OIND-1OIND-3

OIND-5OIND-6

OIND-9

OIND-11

10

10

Supplementary Figure 2. HLA restriction of TCRβ sequences associated with public CD8+ T-cell responses

against Epstein-Barr virus and influenza A virus in sorted samples of virus-reactive CD8+ T cells of all patients

and controls. (A) Frequencies of HLA-A2-restricted public TCRβ sequences in sorted virus-reactive samples of

HLA-A2 positive and negative individuals. (B) Frequencies of HLA-B8/B35-restricted public TCRβ sequences

in sorted virus-reactive samples of HLA-B8/B35 positive and negative individuals. Mann-Whitney U test was

used on united results to compare the occurrence of public TCRβ sequences between individuals carrying the

restricting HLA haplotypes vs. those who did not; *p = 0.004.

AMS

OIND

B

EBV Influenza A virus

Blood CSF Blood CSF Blood CSF Blood CSF0

200

400

600 600

400

200

0

600

400

200

0

600

400

200

0

0

200

400

600

10001500

0

200

400

600

10001500

0

200

400

600

10001500

0

200

400

600

10001500

Blood CSF Blood CSF Blood CSF Blood CSF

CD8+ T cells CD4+ T cells CD8+ T cells CD4+ T cellsp > 0.99 p = 0.31 p = 0.38 p = 0.94

EBV Influenza A virus

CD8+ T cells CD4+ T cells CD8+ T cells CD4+ T cellsp = 0.41 p = 0.41 p = 0.23 p = 0.23

Num

ber o

f uni

que

TCRβ

seq

uenc

esNu

mbe

r of u

niqu

e TC

Rβ s

eque

nces

Supplementary Figure 3. Number of unique Epstein Barr virus (EBV)-reactive and influenza A virus-reactive

TCRβ sequences identified in blood and CSF of patients with multiple sclerosis (MS) (A) and controls with

other inflammatory neurological diseases (OIND) (B). The data points represent the number of unique virus-

reactive TCRβ sequences identified in either compartment in each individual. The bars depict the median of the

groups, which were compared employing Wilcoxon signed rank test.

EBNA

-1 Ig

G tit

er (U

/ml)

VCA

IgG

titer

(U/m

l)

Vira

l loa

d(E

BV c

opy

num

ber p

er 1

06 PBM

C)

MS OIND

A B C** *

MS OIND MS OIND0

1,000

2,000

3,000

0

1,000

2,000

500

1,500

500

1,000

1,500

Supplementary Figure 4. Serum titers of anti-Epstein Barr virus (EBV) antibodies and the peripheral blood

EBV viral load in patients with multiple sclerosis (MS) and controls with other inflammatory neurological

diseases (OIND). (A) Serum levels of IgG anti-EBV nuclear antigen-1 (EBNA-1) antibodies. (B) Serum levels

of IgG anti-viral capsid antigen (VCA) antibodies. (C) EBV viral load in PBMC. The controls OIND-8 and

OIND-9 were not included in the latter analysis due to a shortage of material. The bars represent the median for

each group, and the groups were compared using Mann-Whitney U test; *p<0.05; **p<0.01.

Supplementary Table 1. Summary of productive TCRβ sequences obtained from the cerebrospinal fluid (CSF)

and blood from each study subject.

CSF Blood

Total Unique Total Unique

MS-1 4,968,110 55,428 2,973,206 30,550

MS-2 4,272,636 3,200 211,883 7,365

MS-3 6,520,027 20,052 233,841 9,138

MS-4 7,618,800 19,292 1,009,649 14,960

MS-5 7,877,374 40,298 2,155,363 10,094

MS-6 1,780,093 13,171 2,454,256 31,797

MS-7 1,161,612 16,629 5,176,825 85,525

MS-8 1,553,749 11,149 5,950,035 85,305

MS-9 1,333,129 16,266 6,561,692 57,468

MS-10 3,926,670 26,354 4,668,226 188,877

OIND-1 4,330,148 59,627 7,811,095 16,426

OIND-2 5,694,937 30,663 6,459,855 16,072

OIND-3 2,710,304 72,587 1,554,852 53,100

OIND-4 2,611,033 101,224 1,362,441 61,132

OIND-5 3,249,232 29,649 838,946 29,052

OIND-6 1,810,248 62,761 6,263,135 128,625

OIND-7 1,203,853 10,260 2,972,613 67,238

OIND-8 1,738,143 15,113 4,684,047 79,736

OIND-9 1,514,126 17,171 7,643,686 67,550

OIND-10 1,753,206 15,835 3,364,686 77,710

OIND-11 1,929,633 7,326 4,572,127 106,265

MS: multiple sclerosis; OIND: other inflammatory neurological diseases.

Supplementary Table 2. Previously identified public TCRβ sequences associated with CD8+ T cell responses

against human viruses.

TCRβ CDR3 sequence V J HLA restriction Specificity References

CSARDGTGNGYT 20-1 1-2 A*0201 EBV [1]

CSARDRTGNGYT 20-1 1-2 A*0201 EBV [1]

CSARDRVGNTIY 20-1 1-3 A*0201 EBV [1]

CSARVGVGNTIY 20-1 1-3 A*0201 EBV [1]

CSVGTGGTNEKLF 29-1 1-4 A*0201 EBV [1]

CSSQEGGYGYT 29-1 1-2 A*0201 EBV [1]

CSARDQTGNGYT 20-1 1-2 A*0201 EBV [1]

CSARDRIGNGYT 20-1 1-2 A*0201 EBV [1]

CSARIGVGNTIY 20-1 1-3 A*0201 EBV [1]

CSARSGVGNTIY 20-1 1-3 A*0201 EBV [1]

CASSEGRVSPGELF 2 2-2 A*0201 EBV [1]

CSVGQGGTNEKLF 29-1 1-4 A*0201 EBV [2]

CASSLGQAYEQYF 7-8 2-7 B*0801 EBV [3]

CASSLTGPGDQPQHF 7-9 1-5 B*08 EBV [4]

CSVGAGDYEQYF 29-1 2-7 B*08 EBV [4]

CASSVGQAYEQYF 7-8 2-7 B*08 EBV [4]

CAISTGDSNQPQHF 10-3 1-5 B*3501 EBV [5]

CAIGTGDSNQPQHF 10-3 1-5 B*3501 EBV [5]

CATSTGDSNQPQHF 10-3 1-5 B*3501 EBV [5]

CASSARSGELFF 9 2-2 B*3501/08 EBV [6]

CASSARTGELFF 9 2-2 B*3501 EBV [6]

CASSVRTGELFF 9 2-2 B*3501 EBV [6]

CASRYRDDSYNEQFF 7-9 2-1 B*4405 EBV [7, 8]

CASSSRSSYEQYF 19 2-7 A*0201 Influenza A [9]

CASSIRSSYEQYF 19 2-7 A*0201 Influenza A [9]

CASSMRSSYEQYF 19 2-7 A*0201 Influenza A [9]

CASSTRSTDTQYF 19 2-3 A*0201 Influenza A [9]

CASSMRSTDTQYF 19 2-3 A*0201 Influenza A [9]

CASSIRSAYEQYF 19 2-7 A*0201 Influenza A [9]

CASSTGSYGYTF 19 1-2 A*0201 Influenza A [9]

CASSIGNYGYTF 19 1-2 A*0201 Influenza A [9]

CASSSANYGYT 12-4 1-2 A*0201 CMV [1]

CASSLAPGATNEKLF 7-6 1-4 A*0201 CMV [1]

CASSSAHYGYT 12-4 1-2 A*0201 CMV [1]

CASSLEGYTEAF 27 1-1 A*0201 CMV [1]

CASSSAYYGYT 12-4 1-2 A*0201 CMV [1]

CASSLVGGRYGYT 12-4 1-2 A*0201 CMV [1]

CASSVVNEQF 12-4 2-1 A*0201 CMV [1]

CASSLTSGSPYNEQF 27 1-1 A*0201 CMV [1]

CASSFQGYTEAF 28 1-1 A*0201 CMV [1]

CASRPGTSSYEQYF 28 2-7 B*3508 CMV [10]

CASSPQTGTGGYGYTFG 13-1 1-2 B*0702 CMV [11]

CASSVWGTDTQYF 9 2-3 B*0702 HSV [12]

CASRRQGRDNEQFF 12-4 2-1 B*0702 HSV [12]

CATRIGWGTDTQYF 5-1 2-3 B*0702 HSV [12]

EBV: Epstein-Barr virus; CMV: cytomegalovirus; HSV: Herpes simplex virus.

Supplementary Table 3: Frequencies of previously described public TCRβ sequences in samples from blood,

and in sorted Epstein-Barr virus (EBV)- and Influenza A-reactive samples from patients with multiple sclerosis

(MS) and controls with other inflammatory neurological diseases (OIND).

CDR3 Specificity ID Blood

(%)

Sorted EBV-

reactive

T cells (%)

Sorted

Influenza A-

reactive

T cells (%)

CD8+ CD4+ CD8+ CD4+

CSARDGTGNGYTF EBV; BMLF-1 MS-2 ND 0.01 ND ND ND

CSARDRTGNGYTF EBV; BMLF-1 MS-2 ND 0.11 ND ND ND

CSVGTGGTNEKLFF EBV; BMLF-1 MS-2 0.03 6.50 0.10 ND ND

CSVGQGGTNEKLFF EBV; BMLF-1 MS-2 0.03 1.14 ND ND ND

CSARDGTGNGYTF EBV; BMLF-1 MS-3 ND 0.06 ND ND ND

CSARDRTGNGYTF EBV; BMLF-1 MS-3 ND 0.03 ND ND ND

CSVGTGGTNEKLFF EBV; BMLF-1 MS-3 0.04 3.35 0.01 ND ND

CSARDGTGNGYTF EBV; BMLF-1 MS-5 ND 0.04 ND ND 0.00

CSARDRVGNTIYF EBV; BMLF-1 MS-5 ND 0.04 ND ND ND

CSARVGVGNTIYF EBV; BMLF-1 MS-5 ND 0.02 ND ND ND

CSVGTGGTNEKLFF EBV; BMLF-1 MS-5 0.03 8.00 0.07 ND 0.00

CASSLGQAYEQYF EBV; EBNA-3A MS-8 0.09 0.06 ND 0.04 0.10

CAISTGDSNQPQHF EBV; BZLF-1 MS-8 0.00 0.24 ND ND ND

CAIGTGDSNQPQHF EBV; BZLF-1 MS-8 0.01 0.07 ND ND ND

CATSTGDSNQPQHF EBV; BZLF-1 MS-8 0.01 0.23 ND ND ND

CSARDRTGNGYTF EBV; BMLF-1 MS-9 0.00 0.20 ND ND ND

CSVGTGGTNEKLFF EBV; BMLF-1 MS-9 0.01 0.71 ND ND ND

CSARDGTGNGYTF EBV; BMLF-1 MS-10 0.00 0.08 0.02 ND ND

CSVGAGDYEQYF EBV; BZLF-1 OND-1 ND 0.01 ND ND ND

CSARDGTGNGYTF EBV; BMLF-1 OND-4 0.06 18.9 ND ND ND

CSVGTGGTNEKLFF EBV; BMLF-1 OND-4 0.03 0.26 0.01 ND ND

CSARDRVGNTIYF EBV; BMLF-1 OND-5 0.28 1.90 0.11 ND ND

CSVGTGGTNEKLFF EBV; BMLF-1 OND-5 0.00 0.12 ND ND ND

CSVGQGGTNEKLFF EBV; BMLF-1 OND-5 0.01 0.14 ND ND ND

CSVGAGDYEQYF EBV; BZLF-1 OND-6 0.21 ND ND ND ND

CSARDGTGNGYTF EBV; BMLF-1 OND-7 0.00 0.03 ND ND ND

CSARDRTGNGYTF EBV; BMLF-1 OND-7 0.10 2.40 0.07 ND ND

CSVGTGGTNEKLFF EBV; BMLF-1 OND-7 0.03 0.23 ND ND ND

CSARDRTGNGYTF EBV; BMLF-1 OND-11 0.00 0.02 ND ND ND

CASSIRSSYEQYF Influenza A MS-3 ND ND ND 0.25 ND

CASSIRSSYEQYF Influenza A MS-5 ND ND 0.00 3.87 0.01

CASSSRSSYEQYF Influenza A MS-5 ND ND ND 0.07 0.02

CASSIRSSYEQYF Influenza A MS-7 ND ND ND 0.10 0.04

CASSSRSSYEQYF Influenza A MS-7 ND ND ND 0.05 ND

CASSIRSSYEQYF Influenza A MS-9 ND ND ND 3.02 ND

CASSSRSSYEQYF Influenza A MS-9 ND ND ND 0.18 ND

CASSIRSSYEQYF Influenza A MS-10 0.02 ND ND 2.09 0.08

CASSSRSSYEQYF Influenza A MS-10 ND ND ND 0.12 ND

CASSIRSSYEQYF Influenza A OIND-4 0.01 0.01 ND 0.54 ND

CASSSRSSYEQYF Influenza A OIND-4 ND 0.00 ND 0.11 ND

CASSIRSSYEQYF Influenza A OIND-5 ND ND ND 1.61 ND

CASSIRSAYEQYF Influenza A OIND-5 0.02 ND ND 0.98 0.08

CASSSRSSYEQYF Influenza A OIND-5 0.00 ND ND 0.01 ND

ND: not detected.

Supplementary Table 4. The ten most frequent TCRβ sequences from the cerebrospinal fluid (CSF) of patients

with MS.

CDR3 ID

CSF

(%)

Blood

(%) V J

Reactivity;

phenotypea)

CASSQDRAGGPYGYTF MS-1 1.76 0.07 4-3 1-2

CASSLGRGYTF MS-1 1.53 0.04 5-6 1-2 EBV; CD8+

CASTWGVVAGELFF MS-1 1.25 0.31 6 2-2 EBV; CD8+

CASSPHGGSANVLTF MS-1 1.01 0.06 4-3 2-6

CASSPGTDYGYTF MS-1 0.78 0.01 4-2 1-2

CASSQHTGIPGNTIYF MS-1 0.68 0.01 4-1 1-3 EBV; CD8+

CSARAERGQHF MS-1 0.52 0.02 20-1 1-5 EBV; CD8+

CASSLAYTGELFF MS-1 0.50 0.02 4-2 2-2 EBV; CD8+

CASSPTQGTFYGYTF MS-1 0.47 0.00 4 1-2 EBV; CD8+

CASTSSPLSTEAFF MS-1 0.44 0.01 6 1-1 EBV; CD4+

CSTPRDNAKNTEAFF MS-2 4.17 0.18 29-1 1-1 Influenza A; CD4+

CSVGQGGTNEKLFFb) MS-2 1.63 0.04 29-1 1-4 EBV; CD8+

CSGLKQGGTEAFF MS-2 1.26 1.06 20-1 1-1

CASSQDMTDEITEAFF MS-2 1.12 0.01 4-3 1-1

CSARDTGQGMEKLFF MS-2 0.60 0.07 20-1 1-4 EBV; CD4+

CASGLRQGLTEAFF MS-2 0.52 0.08 12-5 1-1 EBV; CD8+

CSGGEVEKLFF MS-2 0.52 0.01 29-1 1-4

CASSQDRLTVYGYTF MS-2 0.51 0.07 4-3 1-2

CASSQDFTGYTF MS-2 0.46 0.00 4 1-2

CSVGTGGTNEKLFFb) MS-2 0.46 0.04 29-1 1-4 EBV; CD8+

CASSQSVRLGTEAFF MS-3 1.93 0.03 4-3 1-1

CASSQTDRGTYGYTF MS-3 0.95 0.10 5-5 1-2 EBV; CD8+

CASSSSTNVNTEAFF MS-3 0.84 0.01 5-1 1-1

CASSPLQANSPLHF MS-3 0.78 0.06 6 1-6

CASRGGTHRGQDEAFF MS-3 0.77 0.02 5-1 1-1

CSVIQGVIYTF MS-3 0.76 ND 29-1 1-2

CASSQETGSYEQYF MS-3 0.64 0.12 4-1 2-7

CSAREGPATNEKLFF MS-3 0.63 0.01 20-1 1-4 EBV; CD4+

CASSLVGGAGTEAFF MS-3 0.61 0.05 7-8 1-1

CASSPSRQWVVYGYTF MS-3 0.58 ND 4-3 1-2

CSVEDRVYGYTF MS-4 1.38 0.24 29-1 1-2

CSARDRDHNSPLHF MS-4 0.90 0.25 20-1 1-6

CASRTPRGGYTF MS-4 0.66 0.13 6 1-2

CASSPGRSNEKLFF MS-4 0.54 0.00 6 1-4

CSALTGAAEAFF MS-4 0.47 0.09 20-1 1-1

CSARGGGNTDTQYF MS-4 0.35 0.01 20-1 2-3

CSAAGQGTNYGYTF MS-4 0.29 0.02 20-1 1-2 Influenza A; CD8+

CASSQDGPRRTDTQYF MS-4 0.29 0.22 14-1 2-3

CASRGRAATKNTEAFF MS-4 0.22 0.04 13-1 1-1

CASSLEFSYEQYF MS-4 0.20 0.02 4 2-7 Influenza A; CD8+

CSVYRPGGEAFF MS-5 1.73 0.21 29-1 1-1 EBV; CD8+

CSASGPTGANYGYTF MS-5 0.65 0.11 20-1 1-2 EBV; CD8+

CASGLDSPLSNYGYTF MS-5 0.33 0.08 12-5 1-2 EBV; CD4+

CASSTTRHPSEQYF MS-5 0.30 0.17 6 2-7

CSAKLAGGTEQFF MS-5 0.29 0.00 20-1 2-1

CSVGTGGTNEKLFFb) MS-5 0.25 0.04 20-1 1-3 EBV; CD8+

CSAPKQGSDTIYF MS-5 0.23 0.01 29-1 1-4 EBV; CD4+

CSARGDATNEKLFF MS-5 0.21 0.00 20-1 1-4

CSVDQTQADTQYF MS-5 0.20 0.03 29-1 2-3

CASSPGGGITDTQYF MS-5 0.19 0.18 5-6 2-3 EBV; CD8+

CASSARGTQYF MS-6 0.52 0.04 6 2-3 EBV; CD4+

CASSGTYSNQPQHF MS-6 0.47 1.41 12-5 1-5 Influenza A; CD4+

CARQGDRRGGYTF MS-6 0.41 2.32 30-1 1-2

CASSLDRSIPLEQFF MS-6 0.38 0.42 7-9 2

CASMEARDNEQFF MS-6 0.35 1.89 5-6 2-1

CSVGTGLAKNIQYF MS-6 0.34 0.07 29-1 2-4

CASSPRQGMAETQYF MS-6 0.34 0.13 19-1 2-5 EBV; CD8+

CASSSPPGGWVKNIQYF MS-6 0.33 0.03 7/11 2-4

CASSLSTVSMNTEAFF MS-6 0.32 0.64 7/11 1-1

CAISTGGRENTEAFF MS-6 0.31 0.02 10-3 1-1 EBV; CD4+

CASSLEGSGRTYEQYF MS-7 1.18 0.86 11 2-7 Influenza A; CD8+

CASSRYESPSGNGYTF MS-7 0.46 0.07 7-8

CASSPACWGFAGLTVKVCEQFF MS-7 0.37 0.02 3/4/14 2-1

CSVEAGQGSTQYF MS-7 0.33 0.03 29-1 2-4

CASSWDVENEQFF MS-7 0.30 0.07 6 2-1 Influenza A; CD8+

CASSPLGFSYEQYF MS-7 0.28 0.32 7-6 2-7

CASSYSSGEVYNEQFF MS-7 0.26 0.04 6 2-1 Influenza A; CD4+

CASSLGGVGANYGYTF MS-7 0.26 0.04 7-6 1-2

CASARRGDNQPQHF MS-7 0.25 0.02 6 1-5 EBV; CD4+

CASSGGAGLDQPQHF MS-7 0.25 0.00 6 1-5

CASSPQGPTGTSGRAPQNIQYF MS-8 0.86 0.04 3/4/14 2-4

CASSFSAPGTDTQYF MS-8 0.63 0.00 7-3 2-3

CASSAGRPEAFF MS-8 0.62 0.05 11-2 1-1 Influenza A; CD8+

CASGTEAFF MS-8 0.62 0.22 7/11 2-2

CASSLPRTDLTGELFF MS-8 0.59 0.12 6 1-1

CASSLEQKPYEQYF MS-8 0.49 0.08 7-9 2-7 Influenza A; CD8+

CSVDKGPGYTF MS-8 0.39 0.07 29-1 1-2 Influenza A; CD8+

CASSLGQAYEQYF MS-8 0.39 0.12 7-8 2-7

CASSPPLSGGIFGLTNEKLFF MS-8 0.37 0.00 4-2 1-4

CASSTGLAGNIQYF MS-8 0.31 0.08 5-1 2-4

CASSPLPMENTEAFF MS-9 2.85 0.32 18-1 1-1 EBV; CD4+

CASSLYPHEQFF MS-9 0.94 0.34 7-3 2-1

CASSSATGTGRFFYEKLFF MS-9 0.66 0.14 12 1-4

CASSPPRSGTEAFF MS-9 0.44 0.13 18-1 1-1 Influenza A; CD4+

CASSLDEREGLYNEQFF MS-9 0.35 3.12 11 2-1

CASSLLGQGLSEKLFF MS-9 0.24 0.04 5-1 1-4

CASSLPRVQSTPYRDSPYGYTF MS-9 0.21 0.12 3/4/14 1-2

CASMGRDYTF MS-9 0.20 0.10 19-1 1-2 EBV; CD8+

CASSYGLGLEAFF MS-9 0.19 0.07 6 1-1 EBV; CD8+

CASSLEDIYEQYF MS-9 0.19 0.07 11-2 2-7

CASRDAGGAETQYF MS-10 0.93 0.32 6 2-5

CASSPLRGARRETQYF MS-10 0.68 0.53 7/11 2-5

CASSEQGRENEQFF MS-10 0.40 0.10 7-3 2-1

CASSEDPRGLATNEKLFF MS-10 0.38 0.03 6-1 1-4

CASSYPTSGTDTQYF MS-10 0.31 0.16 6 2-3

CASSQNTGELFF MS-10 0.28 0.14 7-6 2-2 Influenza A; CD4+

CASSFDRGRVTDTQYF MS-10 0.23 0.23 19-1 2-3

CSVENPDEKLFF MS-10 0.20 0.00 29-1 1-4

CASSYEGGANSPLHF MS-10 0.18 0.00 6 1-6

CASSGGTGVSGANVLTF MS-10 0.17 0.00 5-1 2-6

a) Denotes whether the same sequence was found in sorted virus-reactive samples.

b) HLA-A2 restricted Epstein-Barr virus (EBV)-associated public TCRs.

ND: not detected.

Supplementary Table 5. The ten most frequent TCRβ sequences from the cerebrospinal fluid (CSF) of controls

with other inflammatory neurological diseases (OIND).

CDR3 ID

CSF

(%)

Blood

(%) V J

Reactivity;

phenotypea)

CASSLSLGQHYGYTF OIND-1 0.66 0.13 7-2 1-1 Influenza A; CD4+

CSARQGRDHTDTQYF OIND-1 0.61 0.02 20-1 1-1 EBV; CD8+

CSVAPAHTFTYEQYF OIND-1 0.36 0.23 29-1 1-1

CSARGTTEAFF OIND-1 0.36 0.13 20-1 1-1 Influenza A; CD8+

CASRTTGTGEDYTF OIND-1 0.33 0.00 6 1-1

CSAISGVLSPMNEQFF OIND-1 0.28 0.01 20-1 1-1 EBV; CD4+

CSARPPGGGGTEAFF OIND-1 0.25 ND 20-1 1-1

CSAGRGTDTQYF OIND-1 0.23 ND 20-1 1-1

CSAIRGSVNNSPLHF OIND-1 0.23 0.01 20-1 1-1

CATMGPGTDTQYF OIND-1 0.22 0.00 15-1 1-1

CASSLDWIGNQPQHF OIND-2 1.44 0.22 7/11 1-5

CASSLDRGAPLHF OIND-2 1.08 0.05 6 1-6

CSVVPAAVYGYTF OIND-2 0.92 0.16 29-1 1-2 EBV; CD8+

CASSQDRSGDTQYF OIND-2 0.75 0.07 4 2-3

CSANPHTDTQYF OIND-2 0.72 0.03 20-1 2-3 Influenza A; CD8+

CASSTGGDGYTF OIND-2 0.59 0.22 6 1-2

CASSDRMNTEAFF OIND-2 0.57 0.27 5-1 1-1

CASTQGRNSPLHF OIND-2 0.55 0.00 6 1-6

CSAPGQLEKLFF OIND-2 0.50 0.00 6 2-3

CASSEGGRGDGNYGYTF OIND-2 0.44 0.16 20-1 1-2

CAISVGAGQGETQYF OIND-3 3.43 34.41 10-3 2-5

CASSLTGSRELFF OIND-3 0.42 0.05 7-3 2-2

CSVWGDGSSYEQYF OIND-3 0.40 2.47 29-1 2-7

CASSLDSSEQYF OIND-3 0.28 0.01 7-8 2-7 EBV; CD4+

CASSLLPSNTGELFF OIND-3 0.27 0.04 5-1 2-2

CASSFRPGQGAGGANVLTF OIND-3 0.25 0.02 12 2-6

CASTVYRGYNTEAFF OIND-3 0.23 0.45 5-6 1-1

CASSLWISGLGEQFF OIND-3 0.19 0.01 7-2 2

CASSSGTGQGETQYF OIND-3 0.19 2.93 11-2 2-5

CASSDRTHDTQYF OIND-3 0.17 0.06 10-1 2-3

CASSHRTENTEAFF OIND-4 0.83 1.13 4-1 1-1

CASSYMGRASNTEAFF OIND-4 0.22 0.06 6 1-1 EBV; CD4+

CASNDRGLDGEQYF OIND-4 0.20 0.04 6 2-7 EBV; CD4+

CASSPRQGPTGELFF OIND-4 0.18 0.06 7-8 2-2 EBV; CD8+

CASSWTGTYQETQYF OIND-4 0.17 0.09 5-6 2-5 EBV; CD8+

CASSLQLAGGLETQYF OIND-4 0.15 0.00 7/11 2-5

CSVEDLGGVDTQYF OIND-4 0.13 0.01 29-1 2-3

CASSLEGNEQFF OIND-4 0.13 0.02 12 2-1 EBV; CD8+

CASRTKGGMNTEAFF OIND-4 0.13 0.04 6 1-1 EBV; CD8+

CASSRQGAYGAGGRYNEQFF OIND-4 0.11 ND 4-2 2-1

CSVDPGTGELFF OIND-5 4.31 11.83 29-1 2-2

CSVGSGEGYEQYF OIND-5 1.45 2.92 29-1 2-7

CSVDSDYEQYF OIND-5 1.28 0.66 29-1 2-7

CASSDSGGVDYGYTF OIND-5 1.13 0.28 6 1-2

CSATGANSYEQYF OIND-5 0.92 6.25 29-1 2-7

CSVGGSFYGYTF OIND-5 0.81 1.33 29-1 1-2

CASSDPAGVFRQPQHF OIND-5 0.71 0.07 6 1-5 EBV; CD4+

CASSLETTSSNTGELFF OIND-5 0.53 0.23 11 2-2 EBV; CD8+

CASSQDPPDTQYF OIND-5 0.44 0.06 14-1 2-3

CASSSPGGANYEQFF OIND-5 0.38 0.25 5-5 2-1 EBV; CD8+

CASSPPPGVKETQYF OIND-6 0.96 0.12 14-1 2-5

CSARSLRTVHNEKLFF OIND-6 0.44 0.06 20-1 1-4

CASIWDRTPPTGVNGYTF OIND-6 0.25 0.02 5 1-2 EBV; CD8+

CASSSYGQETQYF OIND-6 0.24 0.09 7-3 2-5 EBV; CD8+

CASSEWTAPNQPQHF OIND-6 0.20 ND 6-1 1-5

CASSPTSNLGTQYF OIND-6 0.19 0.01 6 2-5

CSVVAGIYGYTF OIND-6 0.17 0.00 29-1 1-2

CASTRGDGTEAFF OIND-6 0.17 0.01 7-9 1-1 EBV; CD4+

CASSQETALNSPLHF OIND-6 0.14 0.07 4-1 1-6 Influenza A;CD8+

CASSLVKRGAYNEQFF OIND-6 0.14 0.03 7-8 2-1 EBV; CD8+

CASSSVGGDTQYF OIND-7 2.86 0.48 18-1 2-3

CASSIPRQGSGYTF OIND-7 1.76 0.08 19-1 1-2

CASSIEGQKNIQYF OIND-7 1.73 0.49 19-1 2-4 Influenza A; CD4+

CASSPSAVGTDTQYF OIND-7 1.66 0.40 6 2-3 EBV; CD4+

CASSPVDPMGQPQHF OIND-7 1.04 0.19 18-1 1-5

CASSITSGSYNEQFF OIND-7 0.93 1.63 19-1 2-1

CASSTTGNTEAFF OIND-7 0.68 0.08 6 1-1

CAGRGTGQRMGYNSPLHF OIND-7 0.58 0.06 6/10 1-6

CASSLEATGAYNEQFF OIND-7 0.56 0.12 11 2-1

CASSFGGGNTDTQYF OIND-7 0.55 0.34 5-1 2-3

CASSYWAAGELFF OIND-8 1.47 1.53 6 2-2 EBV; CD8+

CASSQSMGRTNTGELFF OIND-8 1.34 1.18 23-1 2-2

CASSYLAGDIQYF OIND-8 1.02 0.66 6 2-4 EBV; CD8+

CASSYFSSSYEQYF OIND-8 1.01 0.03 6 2-7

CASSLQALNTEAFF OIND-8 0.59 0.19 7-2 1-1

CASSLAEDSYEQYF OIND-8 0.45 0.62 7-8 2-7

CASSDSGGSNNEQFF OIND-8 0.45 0.30 2-1 2-1

CASRKQGGNYGYTF OIND-8 0.44 0.29 6 1-2

CASSRQPGQGAGGANVLTF OIND-8 0.30 0.09 6/12 2-6

CASSYSPGLAGDEQYF OIND-8 0.26 0.10 6 1-4 Influenza A; CD4+

CAISESGRSTDTQYF OIND-9 0.67 0.09 10-3 2-3 Influenza A; CD4+

CASSLTYSYEQYF OIND-9 0.47 2.93 7-2 2-7

CASRGEQGFRQPQHF OIND-9 0.46 0.02 6 1-5

CSVGTSGTQYF OIND-9 0.36 ND 29-1 2-3

CASSRLQGNTQYF OIND-9 0.32 0.01 18-1 2-3 EBV; CD4+

CASSFREKYEQYF OIND-9 0.31 0.29 7-9 2-7 EBV; CD8+

CASTLAGGHEKLFF OIND-9 0.29 0.01 6 1-4 EBV; CD4+

CAIPAGSMDTGELFF OIND-9 0.24 0.01 10-3 2-2 EBV; CD4+

CASSLLGGTLSTGELFF OIND-9 0.21 0.00 7-3 2-2

CASSFFFIPRTGGNYGYTF OIND-9 0.21 1.47 7/11 1-2 Influenza A; CD4+

CASSLGTGWAGELFF OIND-10 1.63 0.33 7-8 2-2 EBV; CD8+

CASSPDRVRETQYF OIND-10 1.14 0.00 6 2-5

CASSFWGAGGREKLFF OIND-10 0.73 0.03 7-8 1-4

CASSGISGNPYEQYF OIND-10 0.67 0.01 6-1 2-7

CASSLGDTEAFF OIND-10 0.37 0.22 7-9 1-1

CASSARDTFTGELFF OIND-10 0.36 0.15 6 2-2 EBV; CD8+

CASSPLPSEQYF OIND-10 0.35 0.07 18-1 2-7 EBV; CD4+

CASSPWGSNEQFF OIND-10 0.35 0.03 18-1 2-1

CASGRTGSYNEQFF OIND-10 0.30 0.04 6 2-1

CAWSKLGPPDTQYF OIND-10 0.26 0.02 30-1 2-3

CSARDQTSGSSYPETQYF OIND-11 3.01 0.00 20-1 2-5

CASSYLGRDTQYF OIND-11 2.63 0.00 6 2-3

CASSLGDTEAFF OIND-11 2.34 0.00 7-9 1-1

CASGPPGGADGYTF OIND-11 1.77 0.00 12-5 1-2

CASSLVRGRAGELFF OIND-11 1.54 ND 4-1 2-2

CASSPTGLSRGAFF OIND-11 1.35 ND 14-1 1-1

CASSKNTGIRTDTQYF OIND-11 1.34 ND 7-8 2-3

CARSGTGIVNEQFF OIND-11 1.27 0.00 7-2 2-1

CASSQDRREAFF OIND-11 1.06 ND 6 1-1

CASSHQILPGTGPGNTIYF OIND-11 0.97 0.00 14-1 1-3

a) Denotes whether the same sequence was found in sorted virus reactive samples.

ND: not detected.

Supplementary Table 6. Estimated proportions of Varizella zoster virus (VZV)-, Epstein-Barr virus (EBV)-

and Influenza A virus-reactive CD4+ and CD8+ T cells in the cerebrospinal fluid (CSF) and blood of a patient

with VZV encephalitis (OIND-2).

Reactivity CD4+ T cells (%) CD8+ T cells (%)

Blood CSF Blood CSF

VZV 0.94 4.24 2.06 3.56

EBV 0.13 0.92 0.26 0.81

Influenza A virus 0.15 1.02 0.27 0.26

Supplementary Table 7. Numbers of unique productive TCRβ sequences obtained from sorted samples of

Epstein-Barr virus (EBV) and Influenza A reactive CD4+ and CD8+ T cells.

Sequences identified only among

EBV or influenza A reactive T cellsa)

Shared

sequencesb)

EBV CD4+ EBV CD8+ Influenza A

CD4+

Influenza A

CD8+

CD4+ CD8+

MS-1 5,119 (99.3%) 3,422 (94.1%) 565 (95.2%) 362 (59.8%) 23 49

MS-2 5,313 (99.6%) 2,128 (94.3%) 1,226 (97.6%) 293 (79.9%) 20 38

MS-3 3,955 (99.5%) 3,458 (92.2%) 847 (94.0%) 1,207 (83.9%) 15 50

MS-4 3,871 (19.2%) 2,389 (89.0%) 5,600 (76.3%) 40,773 (97.0%) 248 92

MS-5 2,582 (97.1%) 2,270 (90.4%) 2,026 (88.0%) 1,191 (95.3%) 38 64

MS-6 455 (91.0%) 1,016 (96.4%) 399 (87.6%) 403 (81.1%) 12 23

MS-7 312 (95.0%) 276 (81.5%) 1,932 (99.3%) 1,708 (96.5%) 15 25

MS-8 588 (95.8%) 658 (31.1%) 1,899 (95.2%) 1,264 (94.5%) 15 30

MS-9 377 (99.0%) 1,457 (88.1%) 2,465 (99,9%) 726 (93.3%) 8 30

MS-10 1,432 (87.8%) 1,395 (75.3%) 2,722 (96.9%) 1,665 (96.1%) 35 25

OND-1 4,470 (97.4%) 10,317 (97.6%) 17,697 (94.8%) 924 (95.4%) 499 58

OND-2 87 (96.9%) 15,817 (84.2%) 193 (96.8%) 5,032 (91.0%) 3 12

OND-3 481 (91.5%) 1,232 (47.0%) 896 (97.1%) 1,490 (41.2%) 11 85

OND-4 17,234 (99.9%) 7,050 (99.2%) 762 (96.6%) 360 (91.6%) 12 18

OND-5 725 (85.6%) 844 (46.2%) 649 (97.0%) 429 (97.7%) 16 22

OND-6 840 (35.2%) 1,021 (96.4%) 837 (99.5%) 718 (90.6%) 3 19

OND-7 245 (55.4%) 919 (71.2%) 385 (98.5%) 580 (71.7%) 10 54

OND-8 807 (86.0%) 736 (67.9%) 978 (98.1%) 928 (89.9%) 32 33

OND-9 82 (99.4%) 125 (90.0%) 645 (99.9%) 336 (94.4%) 1 6

OND-10 446 (100%) 730 (100%) N/A N/A N/A N/A

OND-11 633 (98.9%) 170 (92.5%) 280 (98.2%) 676 (96.5%) 5 11

a) Sequences exclusively identified in samples of T cells reacting upon stimulation with either virus (the relative

fraction of these sequences is given in brackets).

b) Sequences identified in both samples of T cells reacting with either virus.

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