ῌ,**/ The Japanese Society for AIDS Research /  ECC The Journal of AIDS Research HIV  !"Analysis of Cellular Immune Response on HIV Infection  Ai KAWANA-TACHIKAWA



Division of Infectious Diseases, The Institute of Medical Science,
The University of Tokyo Advanced Clinical Research Center 1 : +*-῍+*3 ,**/

  !"# HIV $%&'( ) *+$,-!.

_!01fb# 3 ;. HLA-B-/ ) HIV-+ CTL$/0! + HIV $%&' CTL

pP3/ 9 Y.2.34A10 ghij1234561.789 , CTL 12

34A0#N HLA-B-/ ) + AV $/3.:;<= ->561?@AB #0!. + 5. , 6 HLA-B-/ ) +0 HIV 4 CD2 ) T ( .C7D.E9FG.H

 + 6$,-!A #N pP301$B/f

IJ.K $&!LM'N

b# SF, .ghij34970# - ;+#HIV  CTL$ +,-./.pP3 HLA-B-/ )$4$Xb'ghi$%&'()*jv8r'U9XW9S #0N Pol 9:. B-/SF,-. VPLDKDFRKY . 0 ;).g1 ¡j DHIV $%-!561.OPQ6$(*+RSTA !-'U9V.

)

WX¢6hj E £.v SF,-.-D0E 0yV PolWX

9:. B-/-+. NPDIVIYQY . - ;). D WX E £.

XW$S !"#+N 0W0SXY.Z HIV (v +.-D-E Nef 9:. B-/-SF,-0 . ++ ;).Q¤) *+.[\'( ]^) T ('`aWXb'U9cXW$S(CTL $_ Y WX¥¦<6g < F £.v SF,-0-Y++F!"#,῍.N CTL  HLA-B-/ )$7M! HLA-B-/ )$%-!. MHC class I d$_eJfb!-' +* g!<§$F,-$780!-# +N B-/-SF,-. $/0

hijkl.m3nopP3A"qr'N HIV ! HLA-B-/ )0# +3 34.w¨ +/4AsU0tr-561\e pP390!J34 13ῌ  SF,-.-D0E \'.$=0! HLA-B-/ fb#'$u$ghijvA%w4Axy'9 CTL) +0 34.w¨ - 34 +3ῌ \e <§©

$_e"qfbSVS' \'-fb$VVS'z{"ªXb# p«*.**+ ; Fisher’s exact testN 0>$ B-/-\'N YU| HIV .&}~'. HIV $/0+. $/0!c D-E .,- HLA-B-/ )! pP3$u.ghijv$()0!

+.ῌ+3 1.ῌ \'.$=0! HLA-B-/ )

A

#N ,ῌ+0 +-ῌ p«*.**+ .¬\ #N # B-/-SF,-| HLA P. MHC-B-/ $_ !Jfb'

0-Y++F .ghijvc HLA-B-/ )<§$CTL pP3$/0!A #N HLA-B-/ *

F,-$Xb# 1.ῌ vs *ῌ, p«*.***+N UbX.

. A r' HLA 90!+Xb!%e

WX HLA-B-/ )?@ B-/-SF,-.-D0E, B-/-$%&'g6,-. 2ῌ \'N +* . HLA-B-/ )+.-D-E, SF,-0-Y++F A­,561Au$®¯0tr

~$_' /  )$_' /  +0 V UbX CTL WX.1234\'U9°. HLA-B-/ ) ~$_' 0  )$_

Bfb'N' +*  . HIV-+ .~A/-! Shiga X$

# | HLA-A,. $_ !Jfb' CTL pP
3 $/0!±²3 B . HIV $,-!0>.
0DEF: ·+*2῍20-3 G¸¹HºI .῍0῍+ 

Fax : *-῍/..3῍/.,1,**/ 5 / » +1 ¼J

A#N HLA-A,. 

$C³$- HLA ´ g6,-. -/ῌ rSµ¨

. 0¶1 T

HLA-A,. A<r'N Z$.pP3 HLA-B-/ .

+*- .- A KAWANA-TACHIKAWA : Analysis of Cellular Immune Response on HIV Infection HLA-A,. 

 !"1#$  Nef+-2+* %RYPLTFGWCF#& , '()*+,- %Y# ./0120- %F# 345 %Nef+-2-,F#  67
ῌ +ῌ ,HIV

HIV+*. % .. #8 HLA-A,. 9:;<& 3-ῌ!" %= ,#$ >?)@?AB HIV CD)*E B 9: Nef+-2-,F ;<&F -*ῌG8 HLA-A,. ";<HIJKLMN!"$ O

PQRS HLA-B-/ TUO HIV CTL VWX?E[\YZ

PQRS HLA-A,. TUO HIV CTL VWX?E Nef+-2-+* YZ

The Journal of AIDS Research Vol. 1

No. ,,**/{j|$ })~6< *90

 HLA-A,.  ++  +*  ,F G/z0)F0+ HLA-A,. ,$ < TAP Gstu-/!" ,A#$ % & '!p(*.*+#% /)-.)/06 6Gst0Nef+-2-,F )*+ HIV  CTL

/ N 12\Gstu9+6 MHC

4-5,-./0 123

HLA-A,. 67

8%9:;6$class I 34:65660$ <MHC class I 3)c heavy chain, b, s<=> HLA-A,.

H !b,m#  ¡ MHC class Iῌ07~)¢ +,ῌ+.  ,F  HLA-A,. })./06 CTL  T })£0/ 3ῌ+0 9 ,F 5 ! ,#8¤6$ %¥9% $ %?@ +#5'&AB 6

B +32* = HIV C6 ,# DEF HLA-A,. GH4+ ]¦O:§~

9dr HIV }) CTL ¨© ;%9g$<%ª Nef+-2-+* F,-./0w]xyz

 -*ῌ IJBDEDK+ Nef+-2-,F O HLA-A,. )LM +*ῌ IN Nef+-2-/C Nef+-2-,F/C X«<)=2#$-# =>B

O5 B= HIV ª`WM Nef+-2-+* <3?~=)Z$ <?@ Nef+-2-,F  Nef+-2-

P%)QRLS TDE Nef+-2-,F )*+ CTL ,-./01234-9=

5 HLA-A,. U Nef+-2-,F )*+234-V QR$+* "¬?~=>g&19Nef+-2-/C, Nef+-2-,F/C ?~= Nef+-2-+*, Nef+-2-,F "?%9LW Nef+-2-,F XYZ

10 HLA-A,.

$ W / @ HIV 

1­ A®¯ !PBMC# )B<°0

 Nef+-2-,F  HLA-A,. [*6C±c T }) !data not shown# HLA-A,. 

$ / @ . @ Nef+-2-,F c IFNg ²d})9\]^_\P`abc%9  

³O´ $o$ 6 /*ῌ  IFNg ²d}))«! -#$ %?@

 Nef+-2-,F )*+ HIV !deg0F) ELISPOT assay DE!+ῌ,max# )µD%¶ - @HIV "Z HLA-A,. )*+f78gNef+-2-+*  Nef+-2-,F ·kGHF

5 , @%9:;6$ cL` Nef+-2-,F  HIV 8 Nef+-2-,F I9 +,*** JIJ?F

%9L#hi)jkc

15 CTL 

 !" +#$ < Nef+-2-/C, Nef+-2-,F/C l HLA-A,. OOmn\ IFNg ²d)¸g¹%c + mM IJ´0$oF%p 15qdr Nef

9KL%9L$ IJ?@ Nef+-2-+*  , &'Gstu9 Y  HIV vL+-2-/C, Nef+-2-,F/C  HLA-A,. 3?~=?NQR$,-./0,

CTL  CTL l

,-./0w]xyz( -1%9:;6$ W

Nef+-2-,F  PBMC M1 CD2  T })

 Nef+-2-+* GN<IJ8¤65%  HLA-A,. 3º»4:6  CD2 HLA-A,.  HIV F Nef+-2-+* Y ¼+*/! ./ #A KAWANA-TACHIKAWA : Analysis of Cellular Immune Response on HIV Infection) +Nef+-2-+* f[gh«2 HIV BC¬ CD2 J T !­J +* "®¯
f[gh Nef+-2-,F >µ?4 Nef+-2-/C°± >+*²++³+*²/ M?  Nef+-2-+* >´?
>¶?4 Nef+-2-,F/C >·? 5
ELISPOT assay mn5+2 ¸f[gh¹
=º»Y¼5 +**῍ 4 ¸°±®¯=º»Y¼5῍#T  Nef+-2-+*



Nef+-2-,F  Nef-!

"#$  % & HLA-A,. '()*+, HIV  CD2  T  !"#$%&'(- ./&012vw xyDz{|Ft()ED

Nef+-2-,F 567 NefT 0} ῌ z{.~t4 F^ HIV!"#$5%28!9:;:<= >SeV? 5@A!Y`Z< Jx./ .&Nef+-2-+*

34 Nef+-2-+* /BC5D

Nef+-2-+* ED CTL

FGHIJ5KL Nef+-2  M ,F N

OPQR -+STUV >WXYZ[ N\] STUV? 5 ^3 >:_`:a!
>I? &=bcd! >T??4 -+ e. I  , e. Y  Nef >-+q k E MHC class I Y Z / .gh5*+ MHC class I '5
4 `Z:YZ Z5

4 -+ e. T  , e. F  Nef >-+T,F? 5 class I Y

CTLNef+-2-,F 5f[ghZ5z{FqHIV ED CD2 J T HIV BCJ CD2 J T 

jGH2 .k , 7#`Z

 +*῍  P.&q k+*, ++? >l , A? mn Nef+-2-,F 567

MHC class I ' J4 b,m4 ()f[gNef+-2-+*!5@iD

()f[ghED CD2 J T 5B0}k MHCI,Y?



3? MHC class I Y Z ()f[Nef 5%2D.op

Nef+-2-+* ED CTL F .&q >l , B?  & Nef+-2-,FHLA-A,. '*+,

h >MHC class Iῌf[ghR? &q D MHC class I Y Z@A F%5 .4 ¡¢£¤k >refold-rs2()*+opFt CTLing? .¥&W=uZ[ghRFtt4 ¥¨ QR./   ©ªF%5+*0 > .0 ?

¦§ MHC class Iῌf[¥MHC classThe Journal of AIDS Research Vol. 1

ῌ ,No. ,,**/

Nef+-2-+* % CTL *'BW: Nef ;< +* ,+*3+*/ M U Nef+-2-+* 9:.2 Nef+-2-,F Q U HLA-A,. xy T ;< ;<JUY ,A Nef,-+I,Y Nef,-+T,FT: SeV jk;< ;<JUY-.P ,B  /+Cr release assay  [TI  +, 

  !"#$%&'( )*+ ,SeV-./0123 MHC *

I 456789: HLA-A*,.*, ;<=>? C @ABCDE'FGHI ,BSP

J3EK'+L,S - A

MNOP+'Q*R ,A,.-BSPhisT: SeV

U V.8 HLA-A*,.*, BWXYZ[\]: HIV-+Nef +'Q*R^_`ab ,Nef+-2-+*

c'd eUY N @ABFG

U b,m ,Nef+-2-b,m ,S - B f]g , hi SeV

T: SeVU

6jk\l:fJBWXY jk;<mnopB A,.-BSPhis J Nef+-2-b,m qg%:rPs ,A,.ῌNef+-2-b,m 4t\] A,.ῌNef+-2-b,mu CDE'FGT:fJBWXY streptavidin-PE-.Y A,.ῌNef+-2-b,m . s ,

ῌ -A,.-BSPhis ,A `abOP b,m ,e-b,m T:fJBvwU A,.ῌNef+-2-b,m  -.

j BT:fJ89 -\]Y.:

Y HLA-A,. xy HIV-+ jkz@{|}~ ,PBMC

  -.Y\]Jj 8kUJf Nef+-2-+* % CD2 xy T ;<9X ,S .

+*1, .1 

A KAWANA-TACHIKAWA : Analysis of Cellular Immune Response on HIV Infection

ῐ .

A,.ῌNef+-2-b,m |Hi}4 HIV-+ !"ª PBMC "« Nef+-2-b,m  SeV  HLA-A,. 
 Nef+-2-b,m  SeV !"() HLA-A,. *+,-/0-1 CTL 2345;<. =>)#$%&'). Nef+-2-+*678+9:)

HLA-A*,.*, ?@+A HIV-+ Env

B5&2CDEFGH4I JEnv/2.-++K LM) b,mJEnv/2.-b,mK  SeV !"#$%

N5H34') ;OP. Nef+-2-+* /0-1 CTL
2345Q Env/2.-b,m &'(),-=)

678+R. Nef+-2-b,m &'()
-67)

/0S. ;678+QTUVW Nef+-2-+* XIYZ&'()[M\]^_`ab Jc /AK d Nef+-2-b,m Q)

edfgh

&'()[M MHC 2i( I b j. /0-1 CTL bd1bkljmnofgh e-b,m. ¬­ e-b,mῌSeV !",) Nef+-2-b,mῌSeV J®K. Env/2.-b,mῌSeV J¯K !"#$%&'( JAK. a
Q Nef+-2-b,mῌSeV J°K. Env/2.-b,mῌSeV J±K.
²³h SeV J´K !" JBK p HLA-A,. *+ T Nef+-2-b,m /0- CTL 2345 /+Cr release assay OP µQ Nef+-2+* XIYZ&'(), Nef+-2-b,m  SeV  HLA-A,. *+,-!"p^qrstb

u. Nef +-2-b , m   SeV ! "n Nef +-2-+* / 0 -CTL 2345b /0-67j Jc / BKv MHC 2i( I  SeV w2B4+K /0-1 CD2 *+ Tx!Wyz`{|Hi}4~n. ,K FGH4ILM) b,m

ῐ /ed&'(. )Q. -K !"+w2B4)

 MHC 2i( I ;`1. HIV /0- CD2 *+ T8-)w2B4)n`{f+nanj῏῎῍ῌ2Y5n`a HIV !"
!"=

. HIV+Q`a /FGH4Inf`anod

CTL F(4IQ!" ¡` CTL ¢{£

1b d. w2B4 Q) d¤¥¦§ j¨©`1. 2Y5©+*2 J .2 K

The Journal of AIDS Research Vol. 1HLA  



No. ,,**/antigen B-/ molecules. AIDS +* : +*1/ῌ+*2-, +330.

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Nakamura T, Iwamoto A : Accumulation of speciﬁc6789:;<.=/ SeV >?@A BCDEFG

amino acid substitutions in HLA-B-/-restricted human>?@A8#" $%8:H!I<#immunodeﬁciency virus type + cytotoxic T lymphocyte
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A, Kaneko Y, Takiguchi M : Identiﬁcation and charac-

bY8+.".lmnef Lo'pq8e

terization of multiple HLA-A,.-restricted HIV-+ CTLfjrstuvw-x yz*L+=-x!_{epitopes : strong epitopes are derived from V regions of;|}~*8 HIV $%."-x

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