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Aleksandr M. Gorin, Yushen Du, Franklin Y. Liu, Tian-Hao Zhang, Hwee L. Ng, Christian Hofmann, William G. Cumberland, Ren Sun, Otto O. Yang
HIV-1 epitopes presented by MHC class I types associated with superior immune containment of viremia have highly constrained fitness landscapes
www.plospathogens.org
www.plospathogens.org
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1 J
0 w
10 0 0 10 381.7133 526.9039 cm
BT
/F6 1 Tf
1 TL
0.006 Tc
0 0 Td
(02-restricted\),)Tj
6.0037 0 Td
(KAFSPEVIPMF)Tj
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(\(KF11,)Tj
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ET
Q
q
1 j
1 J
0 w
6.9998 0 0 6.9998 244.8566 517.5496 cm
BT
/F12 1 Tf
1 TL
0 0 Td
()Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 248.8818 513.9212 cm
BT
/F6 1 Tf
1 TL
0.006 Tc
0 0 Td
(57-restricted\),)Tj
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(and)Tj
1.7575 0 Td
(KRWIILGLNK)Tj
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Q
q
1 j
1 J
0 w
6.9998 0 0 6.9998 486.085 517.5496 cm
BT
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1 TL
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ET
Q
q
1 j
1 J
0 w
10 0 0 10 490.0535 513.9212 cm
BT
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1 TL
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(27-restricted\).)Tj
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(Fig)Tj
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(1)Tj
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(a)Tj
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(full)Tj
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(\(100%)Tj
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(variants)Tj
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(43%\))Tj
2.3074 0 Td
(achieving)Tj
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(the)Tj
1.5023 0 Td
(threshold)Tj
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(frequency)Tj
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(of)Tj
1.0318 0 Td
(2.5x10)Tj
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Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 425.8204 440.3905 cm
BT
/F6 1 Tf
1 TL
0.008 Tc
0 0 Td
(-5)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 434.3811 435.9118 cm
BT
/F6 1 Tf
1 TL
0.006 Tc
0 0 Td
(that)Tj
1.8198 0 Td
(was)Tj
1.7291 0 Td
(considered)Tj
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(adequate)Tj
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(for)Tj
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(virus)Tj
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(production)Tj
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(after)Tj
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(transfection)Tj
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(Table)Tj
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(2)Tj
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(expected,)Tj
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(the)Tj
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(consensus)Tj
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(epitope)Tj
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(sequence)Tj
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(was)Tj
1.7291 0 Td
(overrepresented)Tj
6.8201 0 Td
(in)Tj
1.0545 0 Td
(each)Tj
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(library)Tj
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(because)Tj
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(consensus)Tj
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(amino)Tj
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(acids)Tj
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(were)Tj
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(included)Tj
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(every)Tj
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(degenerate)Tj
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(codon)Tj
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(\()Tj
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(Fig)Tj
1.8595 0 Td
(2A)Tj
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(\).)Tj
1.9842 0 Td
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(proviral)Tj
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(DNA)Tj
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(libraries)Tj
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(transfected)Tj
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(pro-)Tj
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(cells)Tj
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(to)Tj
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(yield)Tj
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(starting)Tj
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(virus)Tj
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(libraries)Tj
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(after)Tj
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(a)Tj
0.6633 0 Td
(week)Tj
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(of)Tj
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(Deep)Tj
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(sequencing)Tj
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(viral)Tj
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(RNA)Tj
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(in)Tj
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(these)Tj
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(libraries)Tj
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(again)Tj
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(demonstrated)Tj
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(that)Tj
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(the)Tj
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(consensus)Tj
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(epitope)Tj
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(pre-)Tj
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(that)Tj
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(variants)Tj
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(plasmid)Tj
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(library)Tj
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(persisted)Tj
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(replication-competent)Tj
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(variants)Tj
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(Table)Tj
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(2)Tj
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0.703 0 Td
(and)Tj
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(Fig)Tj
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(2A)Tj
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(\),)Tj
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(sug-)Tj
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(gesting)Tj
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(that)Tj
1.8141 0 Td
(most)Tj
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(epitope)Tj
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(mutations)Tj
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(were)Tj
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(deleterious)Tj
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(\(36.4)Tj
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(86.6%)Tj
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(single)Tj
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(codon)Tj
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(mutants,)Tj
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1.0432 0 Td
(99.97%)Tj
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1.0375 0 Td
(double)Tj
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(codon)Tj
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(mutants\).)Tj
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(variants)Tj
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(with)Tj
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(a)Tj
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(threshold)Tj
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(frequency)Tj
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0 Tc
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(<)Tj
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0.006 Tc
(10)Tj
ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 217.4173 310.337 cm
BT
/F14 1 Tf
1 TL
0.008 Tc
0 0 Td
[()]TJ
/F6 1 Tf
(4)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 227.622 305.9149 cm
BT
/F6 1 Tf
1 TL
0.006 Tc
0 0 Td
(in)Tj
1.0601 0 Td
(two)Tj
1.7348 0 Td
(experimental)Tj
5.5785 0 Td
(replicates)Tj
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(of)Tj
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(virus)Tj
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(libraries)Tj
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(were)Tj
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(considered)Tj
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(to)Tj
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(be)Tj
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(nonviable,)Tj
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(because)Tj
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(they)Tj
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(tended)Tj
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(decay)Tj
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(if)Tj
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(present)Tj
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(in)Tj
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(only)Tj
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(one)Tj
1.7291 0 Td
(library,)Tj
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(indicating)Tj
4.3654 0 Td
(insufficient)Tj
4.8472 0 Td
(replicative)Tj
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(capacity.)Tj
ET
Q
q
0.45 0.36 0.35 0.01 k
1 j
1 J
0 w
35.9997 251.8106 m
575.9997 251.8106 l
575.9997 251.3106 l
35.9997 251.3106 l
f*
108.214 251.3106 m
108.214 229.3106 l
107.714 229.3106 l
107.714 251.3106 l
f*
107.714 229.3106 m
35.9997 229.3106 l
35.9997 229.8107 l
107.714 229.8107 l
f*
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192.4251 229.3106 l
191.9251 229.3106 l
191.9251 251.3106 l
f*
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108.214 229.3106 l
108.214 229.8107 l
191.9251 229.8107 l
f*
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277.3718 229.3106 l
276.8717 229.3106 l
276.8717 251.3106 l
f*
276.8717 229.3106 m
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192.4251 229.8107 l
276.8717 229.8107 l
f*
386.2414 251.3106 m
386.2414 229.3106 l
385.7414 229.3106 l
385.7414 251.3106 l
f*
385.7414 229.3106 m
277.3718 229.3106 l
277.3718 229.8107 l
385.7414 229.8107 l
f*
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435.5388 229.3106 l
435.0387 229.3106 l
435.0387 251.3106 l
f*
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386.2414 229.3106 l
386.2414 229.8107 l
435.0387 229.8107 l
f*
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531.6038 229.3106 l
531.1037 229.3106 l
531.1037 251.3106 l
f*
531.1037 229.3106 m
435.5388 229.3106 l
435.5388 229.8107 l
531.1037 229.8107 l
f*
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531.6038 229.3106 l
531.6038 229.8107 l
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f*
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108.214 190.2572 l
107.714 190.2572 l
107.714 229.3106 l
f*
107.714 190.2572 m
35.9997 190.2572 l
35.9997 190.7572 l
107.714 190.7572 l
f*
192.4251 229.3106 m
192.4251 190.2572 l
191.9251 190.2572 l
191.9251 229.3106 l
f*
191.9251 190.2572 m
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191.9251 190.7572 l
f*
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f*
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f*
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385.7414 216.2928 l
385.7414 229.3106 l
f*
385.7414 216.2928 m
277.3718 216.2928 l
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385.7414 216.7929 l
f*
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f*
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f*
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531.6038 216.2928 l
531.1037 216.2928 l
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f*
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531.1037 216.7929 l
f*
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f*
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385.7414 203.275 l
385.7414 216.2928 l
f*
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f*
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f*
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f*
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f*
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f*
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f*
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f*
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f*
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f*
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f*
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f*
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f*
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f*
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f*
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108.214 138.1859 l
107.714 138.1859 l
107.714 164.2215 l
f*
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f*
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