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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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