Chapter 8
Major Histocompatibility Complex
Dr. Capers
Kindt • Goldsby • Osborne
Kuby IMMUNOLOGY
Sixth Edition
Chapter 8
The Major Histocompatibility
Complex and Antigen Presentation
Copyright © 2007 by W. H. Freeman and Company
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 antigenpresenting 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 MHC
 Alpha 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 Molecule
 α1 and α2 chain
○ Transmembrane
 β1 and β2 chain
○ transmembrane
Figure b shows top
View 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
complex
 Class II MHC are blue
○ Centromeric end of
HLA complex
Cellular Expression of MHC

MHC Diversity
 Diversity (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 restricted
 Can only recognize antigen presented by
MHC Class I molecules
 Therefore, cells with MHC Class I are called
“taget cells”, killed by cytotoxic T cells

CD4+ TH cells are MHC Class II
restricted
 Cells 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 Pathway
Endogenous

Figure below:
○ (a) shows degradation of misfolded proteing
○ (b) shows intact proteins linked to ubiquitin to
be degraded
Endocytic Pathway
Exogenous