It is known that CD8+ T cell responses also play a
major role in the control of primary influenza virus infection
[4,5]. In mice, CTLs against conserved epitopes contribute
to protective immunity against influenza viruses of various
subtypes [6,7]. Identification of CTL epitopes, especially
conserved epitopes shared by multiple viral strains, might
therefore be a robust vaccine strategy against emerging
influenza epidemics. One could argue that CTLs, being specific
for short immunogenic peptides and being diversified
by the highly polymorphic HLA system, are easier to target
against conserved, and thereby potentially cross-protective,
epitopes. Obviously, it is easier to find conservation in a short
primary peptide sequence, a CTL target, than in a longer
tertiary protein structure, such as a characteristic antibody
target. Also, the HLA-restricted CTL immune system targets
different epitopes in different individuals thereby reducing
the risk of a population-wide virus escape through removal
of highly conserved epitope targets. The flipside of trying
to exploit the potential advantages of HLA-restricted CTL
immunity is that one would have to identify several different
CTL targets to encompass the diversity of the HLA system,
and obtain sufficient coverage of the human population. This
problem, however, appears somewhat alleviated by the recent
discovery that HLA molecules largely can be grouped into
12 different “supertypes” of overlapping specificities [8].