| dc.description.abstract | Background:
One major challenge in the development of an HIV-
1 vaccine is the extreme genetic diversity of the virus. A more
cross-reactive T-cell response would be beneficial in cir-
cumventing this issue, but many aspects of the variant-epitope
CD8
+
T-cell response remain poorly defined. Here, we charac-
terize CD8
+
T-cells specific to 4 immunodominant HIV-1 epi-
topes, and their common variants, to better understand their
cross-reactivity and how this changes over time with progression
to AIDS.
Methods:
Blood samples were collected from HIV
+
female
commercial sex workers from Nairobi, Kenya. Samples were
stimulated for 6 hours with HIV-1 Gag and Envelope peptides,
and IL2, IFNy, TNF, and MIP1B were measured via intracellular
flow cytometry. Each sample was stained with tetramers specific
to each peptide to assess which cells were actively secreting cy-
tokines. Multiple samples were collected from the same patients
over 1–6 years when available.
Results:
This study revealed that the majority of cytokine pro-
duction was by CD8
+
T-cells specific to the stimulating peptide.
Cross-reactivity existed between epitopes and their variants,
particularly with Gag IW9/LW9 epitopes, indicating that those
regions may be better targets for future therapeutic agents. Cy-
tokine production in response to Gag KF11 and KGF peptides
were positively correlated to CD4 count. Production of IL2 was
low or absent in all patients, and more likely produced by CD8lo
cells in response to PMA stimulation.
Conclusion:
Considering the ease with which HIV-1 mutates,
it is important to consider how effective CD8
+
T cell responses
are to these common HIV varia
nts, and how they may change
as disease progresses. This study provides unique insight into
not only how responses to these variants differ, but how but
how they change throughout long-term HIV infection. A better
understanding of the dynamics
of these important responses
will be essential in guiding future vaccine or therapeutic
candidates. | en_US |
