Biology Reference
In-Depth Information
(e.g. viruses, bacteria, fungi, parasites), mutated self-cells (e.g. tumors),
or non-self cells and tissues (e.g. transplants). These foreign and self-
proteins are processed through specialized mechanisms and degraded
to short peptides that are presented on the host cell surface for recog-
nition by the T-cell receptor (TCR).
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The process involves major
histocompatibility complex (MHC) molecules, which bind short pep-
tides and display them to T cells. Peptides presented by MHC mole-
cules originate from intracellular (MHC class I) or extracellular
(MHC class II) proteins.
157
MHC class I bound peptides activate
cytotoxic T cells, resulting in killing of target cells (e.g. infected, neo-
plastic, or transplanted tissues), while MHC class II bound peptides
serve mainly in regulation (initiation, enhancement, and suppression)
of immune responses.
157
The ability of the immune system to respond
to a particular antigen varies based on an individual's pattern of MHC
genes. In humans, MHC molecules are known as human leukocyte
antigen (HLA) class II and I. Each person has only three to six HLA
class I molecules and at least that many HLA class II molecules.
157
MHC genes show extensive polymorphism;
>
800 variants of HLA
500 variants of HLA class II molecules have been char-
acterized.
158,159
MHC molecules have a peptide-binding groove that can bind
peptides in a seemingly non-selective and unrestrained manner.
160
For
example, the number of peptides that can bind to each HLA class I
molecule has been estimated at 1,000-10,000 sequences, or an aver-
age of 0.1%-5.0% of all overlapping 9- and 10-mer peptides spanning
the entire protein sequence.
161
Binding of a peptide to an MHC mole-
cule is a prerequisite for recognition by T cells, but only certain peptides
can bind to a given MHC molecule.
162
However, binding in itself is
not enough. Some peptides are good MHC binders in biochemical
assays, but do not elicit a T-cell immune response.
161,163
probably
because they are not properly processed and presented by MHC mol-
ecules. Thus, T-cell epitopes are a subset of MHC-binding peptides.
163
Determining which peptides bind to a specific MHC molecule is crucial
to understanding the mechanisms of immunity and for vaccine and
drug design.
164
Fortunately, binding affinities of thousands of MHC
ligands have been tested and characterized. Results are available in
class I and
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