3_[Dr. Kusworini] Major Histocompability Complex

8/19/2019 3_[Dr. Kusworini] Major Histocompability Complex

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STRUCTURE, FUNCTION AND

GENETICS OF THE MAJOR HISTOCOMPATIBILITY

COMPLEX

KUSWORINI HANDONO

FACULTY OF MEDICINE, BRAWIJAYAUNIVERSITY



Hours Days

Time after infection

Complement

6 12 1 3 5

NK cells

Phagocytes

Epithelialarriers

!icroe

T lymphocytes

" lymphocytes #ntio$ies

Effector T cells

#$apti%e immunity&nnate immunity

'

Immune Sy!em



Mechanisms in Rheumatology ©2001

Humoral &mmunity



Mechanisms in Rheumatology ©2001

Cellular !e$iate$ &mmunity

Click here to run the animation

http://var/www/apps/conversion/tmp/scratch_6/.%5Cimmune3a.exe

http://var/www/apps/conversion/tmp/scratch_6/.%5Cimmune3a.exe





MAJOR HISTOCOMPATIBILITYCOMPLEX

• MHC m"#e$u#e % & '#y$"()"!e%n !*&! &)e e+()ee"n !*e u)-&$e "- .&)%e!y "- $e##

• T*% m"#e$u#e % en$"e /y *%'*#y ("#ym")(*%$

'ene "n $*)"m""me 0 )e'%"n

• T*e MHC #"$u1)e'%"n %n *um&n % e%'n&!e &Hum&n Leu$"$y!e An!%'en 1 HLA

• In !*e m"ue % e%'n&!e & H2, %n !*e /".%ne &

B"LA, %n !*e "' & DLA, %n 'u%ne& (%' & GPLA, %n!*e )&! & RT3

• T*e)e &)e !4" %5e)en! !y(e "- MHC 'ene ()"u$!$&##e $#& I &n $#& II MHC m"#e$u#e



Chromosome 6

!HC(H)# locus

Centromer

Class&& Class&&

&

Class &

DP D* D+ " C #



T*e Im(")!&n$e "- MHC

m"#e$u#e• P#&y & $en!)&# )"#e %n %mmune )e("ne !" ()"!e%n

&n!%'en 6&$!%.&!e &&(!%.e IR7

• P#&y & $en!)&# )"#e %n $#"n&# e#e$!%"n1m&!u)&!%"n "-T ") B #ym(*"$y!e %n !*ymu &n /"ne m&))"4

• P#&y &n %m(")!&n! )"#e %n !*e !)&n(#&n!&!%"n "-")'&n &n !%ue, 4*en ")'&n &)e !)&n(#&n!e&$)" m&8") HLA #"$u %5e)en$e /e!4een "n")

&n )e$%(%en!, ')&-! )e8e$!%"n % ()"m(!

• P#&y & m&8") )"#e %n $"n-e))%n' u$e(!%/%#%!y !"m&ny %e&e 6&u!"%mmune, $&n$e), %n-e$!%"n e!$7



C#& I MHC M"#e$u#e

• C"n!&%n !4" e(&)&!e ("#y(e(!%e $*&%n 9 $*&%n ::;D &n $*&%n 32 ;D

• T*e $*&%n % %.%e %n!" !*)ee )e'%"n 9 &ne+!)&$e##u#&), !)&nmem/)&ne &n $y!"(#&m%$ )e'%"n

• T*e e+!)&$e##u#&) )e'%"n *& /een u/%.%e %n!" 3,2, &n < "m&%n

• T*e $*&%n, 2 m%$)"'#"/u#%n, en$"e /y & 'ene"u!%e !*e MHC, "n $*)"m""me 3=

• D%!)%/u!%"n 9 &## nu$#e&!e $e## "- !*e /"y

• T*e ()%n$%(&# -un$!%"n 9 !" /%n &n ()een! "-%n!)&$e##u#&) &n!%'en !" (e$%>$ T$ #ym(*"$y!e1T CD?@





C#& II MHC M"#e$u#e

• C"m("e "- !4" n"n$".&#en!#y &"$%&!e("#y(e(!%e $*&%n 9 $*&%n <: ;D &n $*&%n <2 ;D

• B"!* ("#y(e(!%e $*&%n &)e %.%e %n!" !*)ee)e'%"n 9 &n e+!)&$e##u#&), !)&nmem/)&ne &n$y!"(#&m%$ )e'%"n

• T*e e+!)&$e##u#&) )e'%"n "- /"!* !*e &n $*&%n*&.e /een u/%.%e %n!" !4" "m&%n, 3, 2 &n 3,2

• D%!)%/u!%"n 9 B #ym(*"$y!e, m&$)"(*&'e, en)%!%$&n & -e4 "!*e) $e## !y(e 6APC7

• T*e ()%n$%(&# -un$!%"n 9 !" /%n &n ()een! "-e+!)&$e##u#&) &n!%'en !" (e$%>$ T* #ym(*"$y!e1T CD:





Fe&!u)e "- C#& I &n C#& IIMHC M"#e$u#e

Fe&!u)e C#& I MHC C#& II MHCP"#y(e(!%&$*&%n

6::: ;D7

2 m%$)"'#"/u#%n632;D7

6<2<: ;7

62<2 ;D7

L"$&!%"n "-("#ym")>$)e%u

3 &n 2"m&%n 3 &n 3"m&%n

B%n%n' %e-") TCR

< )e'%"n /%nCD?

2 )e'%"n /%nCD:

S%e "- (e(!%e/%n%n' $#e-!

A$$"mm"&!e(e(!%e "- ?33)e%ue

A$$"mm"&!e(e(!%e "- 3< )e%ue ")m")e

N"men$#&!u)e

*um&n

HLAA, HLAB,

HLAC 6$#&%$7

HLADR, HLA

D, HLADP



Gene!%$ O)'&n%&!%"n "- !*e*um&n MHC

• T*e HLA )e'%"n, : ;/, "n !*e 0(23<, %%.%e %n!" $#& I, II &n III )e'%"n

• T*e $#& I )e'%"n en$"e 9 HLAA, B &n C

m"#e$u#e 6$#&%$&# m"#e$u#e7 &n HLAE, F,G,H, J 6n"n $#&%$&# m"#e$u#e7

• T*e $#& II )e'%"n en$"e 9 HLADR, D &nDP m"#e$u#e 6$#&%$&# m"#e$u#e7 &n HLADM &n DO 6n"n $#&%$&# m"#e$u#e7

• T*e $#& III )e'%"n %n$#ue 9 C2, C:, ()"(e)%ne-&$!") B, TNF, TNF, HSP, 23*y)"+y#&e



H,!#N !#-.+ H&/T.C.!P#T&"&)&T0 C.!P)E +E&.N

). C.)11#2 H)#D " C4"#C4#+D

"1

C2

H/P'

# "TN " C E - # H

C)#// && C)#// &&& C)#// &

21.H

a

## # #2 #1#1#1

DP DN D!)!P)!P

2

D. D*

D*

D+

"2 "2 "1 "2"1"1 " "3" "5

""6

"4T#P

1

T#P

2unctional ene

Pseu$ogene



H)# D +egion

"2 #2 "1 #1 # " "2 #2 "1 #1 "1 "2 "3 "4 "5 "6 " "7 "8 #

DP DN D. D* D+

1 3



Gene!%$ O)'&n%&!%"n "- C#& IIHLADR Re'%"n

• C"n!&%n & %n'#e DRA 'ene &n m")e !*&n "neDRB 'ene 6DRB3, DRB2, DRB<, DRB:, DRB=,DRB0, DRB, DRB?, DRB7

• DRB2, DRB0, DRB &n DRB &)e (eu"'ene

• T*e 'ene ()"u$! &)e 9 DR3, DR<,DR:, DR= &n DR?

• T*e $*&%n % n"n ("#ym")(*%$

• T*e $*&%n &)e *%'*#y ("#ym")(*%$, !*u !*eDR $*&%n % )e("n%/#e -") e!e)m%n%n' !*eDR !y(e



Gene!%$ O)'&n%&!%"n "- C#& IIHLAD Re'%"n

• C"n!&%n 2 e! "- 'ene 9 DA3, DB3 &n DA2,DB2

• DA2 &n DB2 &)e (eu"'ene

•A ()"u$! "- !*e DA3 &n DB3, $*&%n &n $*&%n, $"m/%ne !" -")m D m"#e$u#e

• T*e D &n $*&%n &)e ("#ym")(*%$, !*e D $*&%n % !*e m&8") e!e)m%n&n! "- !*e D !y(e

•

Be$&ue D 'ene &)e $""m%n&n!#y e+()ee&n !*e &n $*&%n &)e ("#ym")(*%$, &##"4%n%.%u&# 4*" &)e D *e!e)"y'"!e !" e+()e: %!%n$! D m"#e$u#e /y cis &n trans - (&%)%n'



Gene!%$ O)'&n%&!%"n "- C#& II

HLADP Re'%"n• C"n!&%n 2 e! "- 'ene 9 DPA3, DPB3 &n

DPA2, DPB2

•

DPA2 &n DPB2 &)e (eu"'ene• T*e DPA3 &n DPB3 'ene e!e)m%ne !*e

DP &n $*&%n 4*%$* $"m/%ne !" -")mDP m"#e$u#e

• DP $*&%n %(#&y #%m%!e ("#ym")(*%m

• DP $*&%n % *%'*#y ("#ym")(*%m, &n&((e&) !" e!e)m%ne !*e DP !y(e



HLA N"men$#&!u)e

N"men$#&!u)e "- HLA )e#%e "n 9 Se)"#"'%$&##y /&e !y(%n' 6-") m"#e$u#e7 9

e)"#"'%$ (e$%>$%!%e e>ne /y

&##"&n!%/"%e, & HLAA, B, C, DR &n D!y(eE 9 HLAA2 HLAB2 HLADR: e!$

DNA /&e !y(%n' 6-") 'ene!%$7 9 e!e$!

.&)%&/%#%!y "n DNA euen$e 6&##e#e7 An&##e#e % n&me >)! /y %! #"$u, -"##"4e /y&n &!e)%; &n %! &##e#e num/e)E 9 HLAA23 HLAB2= HLA

DR:3 e!$



NUMBER OF ALLELES IN HLA REGION6DNA /&e Ty(%n'7

LOCUS KNOWN

ALLELESC#& I

HLAA 3=3

HLAB <3

HLAC ?<

C#& II

HLA

DRA

2

HLADRB

2?2

HLA

DA

2





%e&e A"$%&!e W%!* HLAB2

• An;y#"%n' ("n%#y!% 6AS7• Re&$!%.e &)!*)%!% 6ReA7

• U.e%!%

• A)!*)%!% &"$%&!e 4%!* %n&mm&!")y/"4e# %e&e

• A)!*)%!% &"$%&!e 4%!* (")%&%

• Un%5e)n!%&!e "#%'"&)!*)%!%

Hy("!*e% !" e+(#&%n !*e



Hy("!*e% !" e+(#&%n !*e&"$%&!%"n "- (e$%>$ HLA 4%!*

%e&e• P)een!&!%"n "- !*e (&!*"'en%$ (e(!%e

/y HLA m"#e$u#e

• T*ym%$ e#e$!%"n "- T $e## )e$e(!"))e(e)!"%)e "n HLA m"#e$u#e 4%!*

e#-(e(!%e

• C*em%$&# m"%>$&!%"n "- HLAm"#e$u#e, &#!e)%n' !*e%) (e(!%e(e$%>$%!y

• L%n;&'e "- HLA #"$u !" & n"nHLA%e&e&"$%&!e 'ene

• Re'u#&!%"n "- T $e## e.e#"(men!

• C)")e&$!%.e &n!%/"y )e("ne





' 2'' 4'' 6'' 7'' 1''' 12''

12'' 14'' 16'' 17'' 2''' 22'' 24''

24'' 26'' 27'' 3''' 32'' 34'' 36''

9

Class & +egion

H)# E H)# - H)# # H)# H H)# H)#

C2H/P ' TN )T)T Class &&& +egion

H)# : " H)# : C H)# Class & +egion

"2"1

#1#2

DP

#"

D!

6 a c t o r "

C4#

C4"

"1

"2

"3

"8

#

D+

#1

"1#2

"2

D*

T # P

1

T # P 2

Proteasome genes

H)# D ( Class && +egion



PRINCIPLE CHARACTERISTICS OFHLAASSOCIATED DISEASES

• M"! HLA&"$%&!e %e&e &)e &u!"%mmune%n n&!u)e

•

En.%)"nmen!&# -&$!") (#&y & $)%!%$&# )"#e %ne.e#"(men! "- %e&e

• D%e&e u$e(!%/%#%!y % e!e)m%ne /y mu#!%(#e'ene

•

M")e !*&n "ne MHC#%n;e 'ene m&y (#&y & )"#e%n %e&e

• T*e %n%!%&!%n' e.en! &n !*e !&)'e! &u!"&n!%'en&)e un;n"4n -") m"! &u!"%mmune %e&e

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3_[Dr. Kusworini] Major Histocompability Complex

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