Benda Asing Dan MHC

8/13/2019 Benda Asing Dan MHC

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Benda Asing Self dan non-self

MHC

Soni Muhsinin, M.Si


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Major Histocompatibility Complex

(MHC)


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MHC

Kompleks Histokompatibilitas Mayor Cluster gen yang ditemukan disemua mamalia

Produknya berperan dalam membedakan self/non-self

Participant dalam imunitas humoral and seluler

Kerja MHC seperti Antigen Presenting Structures

Di Manusia: MHC ditemukan pada Chromosome 6

Referred to as HLA complex

Di Tikus: MHC ditemukan pada Chromosome 17

Referred to as H-2 complex


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Genes Of MHC Organized In 3 Classes Class I MHC genes

Glycoproteins diekspresikan pada semua sel berinti

Fungsi utama menyajikan untuk diproses Ags to TC

Class II MHC genes

Glycoproteins diekspresikan pada Monosit, sel B, Makrofag

Fungsi utama menyajikan untuk diproses Ags to TH

Class III MHC genes

Memproduksi protein yang berperan dalam sistem imun.

e.g: Sistem Komplemen, Molekul Inflamasi

MHC


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Class I MHC Genes Found In Regions A, B and C InHumans (K and D In Mice)

Class II MHC Genes Found In Regions DR, DP and

DQ (IA and IE In Mice) Class I and Class II MHC Share Structural Features

Both involved in APC

Class III MHC Have No Structural Similarity To Class Iand II

Ex. TNF, heat shock proteins, complement components

Class I, II and III MHC


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Terdiri dari 2 molekul: Rantai (45 kDa), transmembrane

2-microglobulin (12 kDa)

Dihubungkan dengan ikatan Non-kovalen

Gabungan rantai dan 2diperlukan untuk ekspresi permukaan

Rantai terdiri dari 3 domain (1, 2 and 3)

2-microglobulin sama dengan 3

1 dan 2 membentuk tempat untuk Peptide Binding

3 Highly Conserved Among MHC I Molecules

Interacts with CD8 (TC) molecule

Class I MHC Molecule


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Terdiri dari rantai dan Rantai and dihubungkan dengan ikatan non-kovalen

Rantai dan terdiri dari:

1and 2 (chain)

1 and 2 (chain)

1 and 1 membentuk tempat Antigen Binding

CD4 Molecule Binds 2/2 domains

Class II MHC Molecule


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Class I And II Similarity


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Presentasi Antigen


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MHC Products Are Highly Polymorphic

Vary considerably from person to person

However, Crossover Rate Is Low

0.5% crossover rate

Inherited as 2 sets (one from father, one from mother)

Haplotype refers to set from mother or father

MHC Alleles Are Co-dominantly Expressed

Both mother and father alleles are expressed

Inbred Mice Haplotypes Are Designated With Italic

Superscript

Ex. H-2b

Designation refers to entire set of H-2 alleles

MHC Genes Are Polymorphic


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Inheritance Of HLA Haplotypes


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Several Hundred Allelic Variants Have Been Identified InHumans

However, up to 6 MHC I And 12 MHC II Molecules Are

Expressed In An Individual

Enormous Number Of Peptides Needs To Be Presented

Using These MHC Molecules

To Achieve This Task MHC Molecules Are Not Very

Specific For Peptides (Unlike TCR and BCR)

Promiscuous Binding Occurs

A peptide can bind a number of MHC

An MHC molecule can bind numerous peptides

Class I And II Specificity


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MHC Is One Of The Most Polymorphic ComplexesKnown

Alleles Can Differ Up To 20 a/a

Class I Alleles In Humans: 240 A, 470 B, 110 C

Class II Alleles In Humans: HLA-DR 350 , 2 !

HLA-DR

genes vary from 2-9 in different individuals!!!,

1 gene (can combine with all productsincreasing number of APC molecules)

DP (2 , 2 ) and DQ (2 , 3 )

Class I And II Diversity And

Polymorphism


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Documents

Benda Asing Dan MHC