Biology Reference
In-Depth Information
The initial success of the research with synthetic peptides pre-
sented an attractive opportunity to develop theoretical approaches for
the prediction of B- and T-cell-specific antigenic epitopes within pro-
teins
48,49
so that these epitopes could be used to design proteins with
desired immunological properties. Although not very accurate, the
computational approaches were used extensively by many laboratories
to identify antigenic sites in proteins. Subsequently, development of
automated methods for peptide synthesis allowed epitope identifica-
tion through total scanning of proteins with overlapping synthetic
peptides.
50,51
Although often efficient, this “brute force” approach to
protein scanning was wasteful and limited to identification of contin-
uous linear antigenic epitopes. It was also inadequate for identifica-
tion of conformation-dependent “split” epitopes, which are often
involved in virus neutralization.
Recognizing the need for more accurate computational approaches
to epitope prediction, many laboratories undertook research efforts
associated with immunological studies. Subsequently, advances in the
identification of mechanisms of antigen presentation and recognition
drastically accelerated progress in the development of sophisticated
computational techniques for the prediction of T-cell epitopes.
48,49
Unfortunately, computational approaches to B-cell epitope prediction
did not receive proper development and remain either simplistic or
dependent on a comprehensive knowledge of protein structure,
52,53
which is rarely available. Despite the limited efficacy of these approaches,
many antigenic epitopes were nevertheless identified and used in pro-
tein engineering experiments. It was discovered that short antigenic
epitopes, which can be modeled with synthetic peptides, can usually
be reliably reproduced in a functional form when inserted into recom-
binant proteins.
54-59
This important feature made antigenic epitopes
attractive building blocks for the “structural” design of proteins with
predetermined immunological properties.
Two approaches to structural design using short antigenic epi-
topes to construct immunologically active proteins have been devised
for the development of new antigenic targets for serologic assays and
vaccine candidates. One approach, based on construction of com-
pletely artificial antigens (multiple epitope proteins [MEP]) built of
