Major Histocompatibility Complex

More than One Class of MHC

There are two major classes of MHC molecules, both of which consist of an and a
chain, but from different sources. MHC class I molecules (MHC I) consist of one membrane-
spanning chain (hea! chain) produced b! MHC genes, and one chain (light chain or "-
microglobulin) produced b! the "-microglobulin gene. MHC class II molecules (MHC II)
consist of two membrane-spanning chains, and , of similar si#e and both produced b!
MHC genes. In each case, the MHC molecule has a grooe that binds a peptide, which it can
then present at the cell surface to a T cell to elicit an immune response, because T cells onl!
recognise antigens as comple$es with MHC molecules. The two classes of MHC proteins
differ not onl! in their structure, but more importantl! in their functional roles within the
immune s!stem% the two t!pes of MHC molecules are specialised to present different t!pes
of antigens, thereb! eliciting different responses.

MHC class I

MHC I gl!coproteins are present on almost eer! cell in the bod!, acting to present
endogenous antigens that originate from the c!toplasm. These antigens include not onl! self-
proteins, but also foreign proteins produced within the cell, such as iral proteins that ta&e
oer the cell's machiner! in order to replicate the irus. (hen these proteins become
degraded, the peptide fragments can be transported to the endoplasmic reticulum, where the!
can bind to MHC I proteins, before being transported ia the )olgi apparatus to the cell
surface. *nce at the cell surface, the membrane-bound MHC I protein displa!s the antigen
for recognition b! special immune cells &nown as c!toto$ic T cell l!mphoc!tes. MHC I
proteins wor& to present the t!pes of proteins being s!nthesised within a cell, which can then
be monitored b! &iller T cells as part of a sureillance s!stem that identifies and destro!s an!
cell with oer-abundant or unfamiliar peptide antigens, such as malignant cells or those
harbouring iruses.

MHC class II

MHC II gl!coproteins are onl! present on specialised antigen-presenting immune
cells, including macrophages that engulf foreign particles such as bacteria, dendritic cells that
present antigen to T cells, and + cells that produce antibodies. MHC II proteins present
e$ogenous antigens that originate e$tracellularl! from foreign bodies such as bacteria. ,pon
encountering a pathogenic organism, proteins from the pathogen can be degraded into peptide
fragments b! the antigen-presenting cell, which then se-uesters these fragments into the
endosome so the! can bind to MHC II proteins, before being transported to the cell surface.
*nce at the cell surface, the membrane-bound MHC II protein displa!s the antigen for
recognition b! a different t!pe of T cell, namel! the helper T cell l!mphoc!te.
These helper T cells are actiated upon binding to macrophage or dendritic cell MHC II-
antigen, causing the release of l!mpho&ines that attract other cells to the area of infection in
an attempt to confine and destro! the antigenic material. In addition, the binding of helper T
cells to + cell MHC II-antigen stimulates the deelopment of a clone of antibod!-producing
cells against the antigenic material.

Major differences between MHC classes I and II

MHC class I MHC class II
Comprised of an MHC-encoded
chain and a "-microglobulin
chain
Comprised of MHC-encoded
and chains
.resent on most cells .resent onl! on antigen-
presenting cells
+ind endogenous antigens
s!nthesi#ed in a cell
+inds e$ogenous antigens
.resent antigen to c!toto$ic
T cell l!mphoc!tes
.resent antigen to helper T cell
l!mphoc!tes
+ind C/0 adhesion molecules
on c!toto$ic T cells
+ind C/1 adhesion molecules
on helper T cells
.resence of foreign or oer-
abundant antigens targets cell
for destruction
.resence of foreign antigens
induces antibod! production,
and attracts immune cells to
area of infection
The immune s!stem has seeral wa!s of protecting !our bod! against inasion b!
iruses, bacteria, parasites and an! other foreign intruder or cancerous cell. The first line of
defence is mounted b! an innate immune response consisting of barriers such as s&in, tears,
salia and mucus, as well as an inflammator! response. This is followed closel! b! defensie
mechanisms mounted b! adaptie immune responses that are more specific for the inading
intruder. 2daptie immunit! includes both a humoral response produced b! antibodies, and a
cell-mediated response produced b! T cells that hae the abilit! to destro! other cells. The
cell-mediated adaptie immune response is regulated b! the major histocompatibilit!
comple$ (MHC), so named because it is responsible for graft rejection, or tissue
compatibilit!. Indiiduals identical for this region can e$change grafts more successfull!
than those with different MHC combinations, which is not an eas! tas& to find considering
that the diersit! of MHC combinations is e$tensie, such that there is on aerage roughl! a
345 difference between an! two unrelated indiiduals. Howeer, this diersit! in MHC
proteins has a protectie function, ma&ing it more difficult for an inading pathogen to elude
the host immune s!stem. 2 major role of the MHC is to bind small peptides and to present
them to the cell surface where the antigen can be recognised b! T cell receptors, the topic of
ne$t month's .rotein-of-the-Month.

MHC, a Means of Antigen Processing

In humans, the MHC genes encode the human leu&oc!te antigens (H62s) on the cell
surface. .roteins inside the cell are bro&en down into short fragments that can be displa!ed
as peptide antigens b! MHC molecules on the surface of the cell. MHC molecules displa!
both 7self' peptides deried from their own proteins, and foreign peptides deried from
inading pathogens. The immune s!stem is constantl! monitoring the surfaces of cells, and
the MHC-presented peptides help immune cells to discriminate between normal antigens on
the surface of all cells, and those that are foreign and potentiall! dangerous. The immune
s!stem also monitors the amount of MHC-presented antigens, which helps them to target and
destro! cancerous cells that often displa! increased amounts of self-antigens. In humans,
the MHC genes encode the human leu&oc!te antigens (H62s) on the cell surface. .roteins
inside the cell are bro&en down into short fragments that can be displa!ed as peptide antigens
b! MHC molecules on the surface of the cell. MHC molecules displa! both 7self' peptides
deried from their own proteins, and foreign peptides deried from inading pathogens. The
immune s!stem is constantl! monitoring the surfaces of cells, and the MHC-presented
peptides help immune cells to discriminate between normal antigens on the surface of all
cells, and those that are foreign and potentiall! dangerous. The immune s!stem also monitors
the amount of MHC-presented antigens, which helps them to target and destro! cancerous
cells that often displa! increased amounts of self-antigens.
MHC proteins hae the abilit! to bind to seeral different peptides, which is necessar!
as there are a ast number of potential peptide targets, and onl! a limited number of MHC
proteins. 8urthermore, the different peptides that an MHC protein can bind are often
structurall! different from one another. This is an unusual propert! for a protein, and ma&es
MHC molecules er! different from other immune s!stem proteins such as antibodies and T
cell receptors, both of which show much greater specificit! for their targets. MHC molecules
are able to bind to such dierse peptides, because both the MHC binding poc&et and the
peptides are relatiel! fle$ible, the latter because of their small si#e. In addition, water
molecules can fill in the gaps between the MHC molecule and its peptide to improe its fit.