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20
15
10
5
0
-5
-10
-15
-20
Fig. 3.
Predicted potential for immunogenicity of selected T-cell epitope clusters. This analy-
sis was performed as previously described; however, the target proteins in this example are
short peptides that are known to be highly immunogenic epitopes. We used the EpiMatrix
prediction matrices for eight class II alleles that are representative of more than 98% of human
populations. We compared the epitopes to our random peptide standard by summing the total
number of EpiMatrix scores for each frame (9 amino acids) that was above an accepted cutoff
for immunogenicity (>1.67), and measured the difference between the scores for “random”
proteins and test proteins.
Well-described “promiscuous epitopes” tend to score above 10 on our immuno-
genicity scale. The promiscuous tetanus toxin epitope 825-850 scores +15 and an-
other well-known epitope from tetanus (peptide 947-967) scores +17.3. Influenza
HA peptide 307-319 scores +17.6 on the immunogenicity scale (Fig. 3). These pep-
tides are so promiscuous that they are frequently used as positive controls in T-cell
activity assays.
After initial exposure to an immunogen, an expanded population of memory
T cells is established that is able to respond more rapidly, efficiently, and in greater
numbers on subsequent exposure. Since the presence of the epitope bound in the
MHC cleft is the trigger for a protective immune response, epitope-driven ap-
proaches to reducing the immunogenicity of therapeutic proteins have focused on
modifying this response by reducing the ability of peptides from therapeutic proteins
to bind to MHC.
