Biology of Disease

PRODUCTION OF A SPECIFIC IMMUNE RESPONSE

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Activation of T lymphocytes

The manner in which T lymphocytes recognize foreign epitopes is rather more
complex than that used by their B lymphocyte counterparts, as the receptors
on T cells are unable to bind to epitopes on ‘native’ proteins. Instead, peptides
derived from the foreign protein are ‘presented’ to them on the surfaces of
other host cells, bound to membrane proteins encoded by a genetic region
called the Major Histocompatibility Complex (MHC). In humans, this genetic
region is found on chromosome 6. The proteins encoded by the MHC include
two classes of membrane proteins. Class I proteins are found on all nucleated
cells in the body. They consist of a single polypeptide, the @ chain, which is
associated with a smaller protein called A 2 microglobulin (A 2 M) that is not
encoded within the MHC. Class II proteins are found on only a few cell types
and are made up of two polypeptides, @ and A, both encoded within the MHC.
Both Class I and II proteins have grooves that can bind a foreign peptide in an
extended form (Figures 4.22and4.23). The peptide-binding groove is formed
by the @ 1 and @ 2 domains of the Class I molecule and the @ 1 and A 1 domains
of the Class II molecule, while these structures are supported, in the Class I
molecule by the @ 3 domain and the A 2 M, and in the Class II molecules by the
@ 2 and A 2 domains.

The requirement to have foreign peptides presented by different MHC
molecules to TC and TH cells can be explained by looking at their roles in vivo.

Activation of TC cells

The role of TCcells is, ultimately, to destroy virus-infected cells. Since all
nucleated cells are susceptible to such infections, MHC encoded Class I
molecules are required by these cells to present endogenously produced
viral peptides to TC cells. Thus, viral protein produced within the cytoplasm
of an infected cell may be hydrolyzed to produce short peptides, about 8–12
amino acid residues in length. These peptides are then transported across the
endoplasmic reticulum where they become attached to Class I proteins and
the complex transported to the surface of the cell membrane in Golgi vesicles.

Membrane

Achain

B2 microglobulin

A)

Figure 4.22 Structure of an MHC Class I molecule

shown (A) diagrammatically and (B) molecular

model showing a bound peptide (red) PDB file

1KJV.

B)

Membrane

A)

Achain B chain

Figure 4.23 Structure of an MHC Class
II molecule shown (A) diagrammatically
and (B) molecular model showing bound
peptide (red) PDB file 1MUJ.

B)