T CELLS RECOGNIZE PEPTIDE FRAGMENTS BOUND TO MHC MOLECULES

Rapid Reference Box 7

CD2 Receptor for CD58 and CD48, expressed by T cells.
CD11a LFA-1 expressed by T, B, and NK cells,
monocyte/macrophages, and granulocytes.
CD28 binds CD80 and CD86, expressed by subpopulations
of T cells and activated B cells.
CD40 binds CD154, co-stimulatory, expressed by B cells,
monocyte/macrophages, and FDCs.
CD45 leukocyte common antigen expressed by populations
of T, B, and NK cells, and monocyte/macrophages.
CD54 ICAM-1 expressed by T, B, and NK cells,
monocyte/macrophages, granulocytes, platelets, DCs, and
other cells.
CD58 a ligand for CD2.
CD80 B7-1, expressed by subpopulations of activated B and
T cells and monocyte/macrophages, and binds CD28 and
CD152.
CD86 B7-2, expressed by activated B cells and
monocyte/macrophages, and binds CD28 and CD152.
CD152 CTLA-4, binds CD80 and CD86, a downregulatory
signaling molecule that competes with CD28 for ligation of
B7 on APCs, expressed by a subpopulation of activated T
cells.
CD154 CD40 ligand (CD40L).
(APC, antigen-presenting cell; CR, complement receptor; DC, dendritic
cell; FDC, follicular dendritic cell; ICAM-1, intercellular adhesion
molecule-1; LCA, leukocyte common antigen; LFA, lymphocyte
functional antigen)

DCs ARE CRUCIAL FOR INITIATING RESPONSES DCs,

which are found in abundance in the T cell areas of lymph

nodes and spleen, are the most effective cells for the initial
activation of naive T cells. They pick up antigens in
peripheral tissues, then migrate to lymph nodes, where
they express high levels of adhesion and co-stimulatory
molecules, as well as MHC class II molecules, which
interact with the TCR and CD4 on TH cells.
Once they have migrated, DCs stop synthesizing MHC
class II molecules, but maintain high levels of stable
expression of MHC class II molecules containing peptides
from antigens derived from the tissue where the DCs
originated.
Interdigitating DCs are believed to be the major APCs
involved in primary immune responses because they induce
T cell proliferation more effectively than any other APC.
Remarkably, DCs are able to present internalized antigens to T cells via MHC class I as well as class II molecules, in a phenomenon called cross-presentation. This
results in activation of cytotoxic T lymphocytes (CTLs),
which are then available for killing of infected cells.
Macrophages and B cells express appropriate costimulatory molecules for activation of naive T cells only
upon infection. Macrophages:
ingest microbes and particulate antigens;
digest them in phagolysosomes; and
present fragments at the cell surface on MHC
molecules.

Q. A number of bacterial components enhance the expression of MHC molecules and co-stimulatory molecules on
macrophages. What effect would you expect this to have on
the immune response? Would it be advantageous for the
individual?
A. In the presence of infection, the action of the microbial
components would enhance the ability of macrophages to
present antigen to T cells. This would generally be advantageous because it would allow the immune system to respond
more effectively to the infection. However, in some circumstances it might be disadvantageous because microbial components would also enhance unwanted immune responses such
as autoimmune reactions.

B cells can:
bind to a specific antigen through surface IgM or IgD;
internalize it; and
then degrade it into peptides, which associate with
MHC class II molecules.
If antigen concentrations are very low, B cells with highaffinity antigen receptors (IgM or IgD) are the most
effective APC because other APCs simply cannot capture
enough antigen. Therefore, for secondary responses,
when the number of antigen-specific B cells is high, B cells
may be a major type of APC.
B cells do not normally express co-stimulatory molecules such as B7, but these can be induced by bacterial
constituents.
The properties and functions of some APCs are
summarized in Figs 7.3 and 7.4.

A series of molecular interactions ensures

highly specific antigen recognition by T cells

Antigens are processed before they are presented

to T cells
Antigen processing involves degrading the antigen into
peptide fragments. The vast majority of epitopes recognized by T cells are fragments from a peptide chain (see
Chapter 5).
Only a minority of peptide fragments from a protein
antigen are able to bind to a particular MHC molecule.
Furthermore, different MHC molecules bind different
sets of peptides (see Chapter 5). For example, studies
using a viral antigen that is recognized by mouse strains of
several different haplotypes (that is, having different
MHC molecules) showed that TH cells from each
haplotype recognized a distinct peptide from that antigen
(Fig. 7.5). This depended largely on whether the strain
possessed an MHC class II molecule that could bind to the
particular peptide.
Q. The APCs of BALB/c mice present peptide 1026 of the
-repressor, whereas APCs of the C57BL/6 mouse present
peptide 7086 (see Fig. 7.5). Which of these peptides would
be presented by APCs of an F1 mouse derived from a cross
of these two strains?
A. Because MHC molecules are co-dominantly expressed, the
APCs in the F1 strain will express both types of APC, and will
therefore be able to present both peptides.

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