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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
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
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
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”
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
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