Chapter 8

Major Histocompatibility Complex

Dr. Reena

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 chain
Transmembrane
Encoded by A, B,

and C regions in
human MHC
complex
Beta 2-

microglobulin
Encoded by highly

conserved gene on
different
chromosome

Class II Molecule
1 and 2 chain
Transmembrane

1 and 2 chain
transmembrane

Figurebshowstop
Viewofpeptidecleft

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

Comparison of Class I and Class II

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 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)

Class I and Class II

Antigen Acquisition

MHC Restriction
Mice immunized
with lymphocytic
choriomenigitis virus
(LCM)
Animals 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