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Chapter 8 Major Histocompatibility Complex Dr. Capers.

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Chapter 8 Major Histocompatibility Complex Dr. Capers
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Chapter 8

Major Histocompatibility Complex

Dr. Capers

Kuby IMMUNOLOGYSixth Edition

Chapter 8The Major Histocompatibility

Complex and Antigen Presentation

Copyright © 2007 by W. H. Freeman and Company

Kindt • Goldsby • Osborne

Antibodies can recognize antigen alone T-cell receptors can only recognize

antigen that has been processed and presented by Major Histocompatibility Complex (MHC)

Involves:- Antigen processing- Antigen presentation

Inheritance of MHC

MHC coded by cluster of genes○ Rejection of foreign tissue is due to immune

response against cell surface molecules, histocompatibility antigens

Inheritance of MHC Collection of genes on chromosome 6 in

humans (HLA complex) and chromosome 17 in mice (H-2 complex)

○ Class I MHC genes- Encode glycoproteins expressed on all nucleated cells

○ Class II MHC genes- Encode glycoproteins expressed on antigen-

presenting cells (macrophages, B cells, dendritic cells)

○ Class III MHC genes- Encode various products involved in complement and

inflammation

Inheritance of MHC

Inheritance of MHC

Many different alleles exist at each locus among the population

○ Each set of alleles is called a haplotype○ Genes of MHC lie close together so crossing

over during meiosis occurs infrequently○ Individual inherits one haplotype from mom,

one from dad- Many in the population are heterozygous- Alleles are codominant so expressed

simultaneously

Inheritance of MHC

Inbred strains will express identical haplotypes – homozygous

○ Inbred mice are solid colors

Inheritance of MHC

MHC molecules

Both Class I and Class II are membrane-bound glycoproteins

○ Antigen-presenting molecules

Class I MHCAlpha α chain

○ Transmembrane○ Encoded by A, B, and C

regions in human MHC complex

Beta β2-microglobulin○ Encoded by highly

conserved gene on different chromosome

Class II Moleculeα1 and α2 chain

○ Transmembrane

β1 and β2 chain

○ transmembrane

Figure b shows topView of peptide cleft

Every individual expresses small number of different Class I and Class II

○ Limited number of MHC must be able to present enormous array of different antigens

○ MHC does not display specificity of Antibodies○ MHC is “promiscuous”

Peptide Interactions with MHC

Generation of B-cell receptors (antibodies) and T-cell receptors is dynamic, changing over-time

○ Gene rearrangement

In contrast, MHC molecules are fixed in the genes

○ Differences in population due to large number of alleles

- In humans, ~370 A alleles, 660 B alleles, 190 C alleles

Location of genes Human

Class I MHC are red○ Telomeric end of HLA

complexClass II MHC are blue

○ Centromeric end of HLA complex

Cellular Expression of MHC

MHC DiversityDiversity (polymorphism) helps to protect a

species from wide range of infectious diseases

Certain alleles make individuals more susceptible to diseases

Example, polymorphism in cheetah is limited, due to bottleneck effect

MHC Restriction

CD8+ Tc cells are MHC Class I restrictedCan only recognize antigen presented by

MHC Class I moleculesTherefore, cells with MHC Class I are called

“taget cells”, killed by cytotoxic T cells

CD4+ TH cells are MHC Class II restrictedCells with MHC Class II are called antigen-

presenting cells (APCs)

MHC Restriction Mice immunized

with lymphocytic choriomenigitis virus (LCM)

Animal’s spleen cells were extracted (containing Tc cells)

Antigen Presenting Pathways Cystolic Pathway

○ Endogeneous antigens – produced in cell, in infected cell

○ Antigens presented on MHC Class I to Tc cells

Endocytic Pathway○ Exogeneous antigen – taken in by

endocytosis by antigen-presenting cells and presented to TH cells by MHC Class II

Cystolic PathwayEndogenous Figure below:

○ (a) shows degradation of misfolded proteing○ (b) shows intact proteins linked to ubiquitin to

be degraded

Endocytic PathwayExogenous


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