Evolutionary Principles in Viral Epitopes - Mathematical Methods and Models in Biomedicine - page 56

Evolutionary Principles in Viral Epitopes

Yaakov Maman, Alexandra Agranovich, Tal Vider Shalit, and
Yoram Louzoun

1 Introduction: Can We Learn from Epitope Distribution

on Viral Evolution?

The infection of a cell by a virus elicits a Cytotoxic T Lymphocyte (CTL) response
to viral peptides presented by the Major Histocompatibility Complex class I
molecules [ 6 , 20 ]. Such a CTL response plays a critical role in the host's anti-
viral immune response [ 39 ]. This role is suggested by studies indicating a drop of
viral loads and the relief of the acute infection symptoms following the emergence
of virus-specific CTLs [ 8 ], as well as by data from CTL depleted animal models
[ 33 , 41 ]. The CTL response is also associated with a rapid selection of viral CTL
escape variants [ 23 , 34 ]. In the last few years we have applied an immunomic
methodology combining genomic data and multiple bioinformatic tools to study
the anti-viral CTL response [ 5 , 19 , 28 , 35 , 38 , 55 - 57 ] and found that viruses
selectively mutate proteins inducing the highest danger to their survival. We here
summarize these results, and propose some general conclusions regarding the
selective forces affecting viruses and their human host.
In general, CTL epitopes are short peptides that can be recognized by CTLs
when presented on MHC-I molecules, as will be further explained. These epi-
topes originate from short peptides cleaved by the proteasome [ 48 ] that can pass
through the transporter associated with antigen processing (TAP) and associate
non-covalently with the groove of MHC-I molecules. A large fraction of these

Y. M a m a n
The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University,
Ramat Gan, 52900 Israel
A. Agranovich ￿ T.V. Shalit ￿ Y. Louzoun ( )
Department of Mathematics and Gonda Brain Research Center, Bar-Ilan University,
Ramat Gan 52900, Israel
e-mail: [e-mail]