| dc.description.abstract | Background: One major challenge in the creation of an HIV-1
vaccine is the extreme genetic diversity of the virus. It is thought
that a more cross-reactive T-cell response would be beneficial in
circumventing this issue. Despite this, little is known about the
characteristics of these responses in nature, and many aspects of
the variant-epitope CD8+ T-cell response remain poorly defined.
Here, we characterize CD8 + T-cells specific to an immunodominant
HIV-1 epitope, IW9, and 2 of its variants, to better
understand the level of cross-reactivity between them.
Methods: Using samples from the Pumwani commercial sexworker
cohort in Nairobi, Kenya, individuals positive for either
HLA-B*4201 or HLA-B*0702 were screened for binding to tetramers
specific for the IW9 epitope and 2 variants. Analysis of
epitope specific cytokine expression and proliferation was performed
to determine the level of functional cross-reactivity of
the variant-specific T-cell pools. Additionally, heteroduplex
mobility assays (HDMAs) were performed to determine differences
in TCR usage among the T-cells responding to each
variant.
Results: Tetramer co-staining experiments indicate that there is
some cross-reactivity among these variants, shown by strong
double-positive populations in flow cytometry. However, in
some cases, separate cell populations are being recognized by
each variant. Proliferation assays show that T-cells stimulated by
one variant can be recognized by tetramers specific to another
variant. HDMAs revealed that there are differences in TCR usage
among variant-specific CD8 + T-cells both at the family and clonotype
level. This may suggest a combination of public and private
clonotype usage, which could explain the differences in
cross-reactivity and functionality.
Conclusion: In order to create a T-cell vaccine that can target and
produce protective immune responses, it will be necessary to
fully understand the nature of cross-reactive responses. This
study has shown evidence that cross reactivity exists within the
IW9 epitope, and that there are several factors that may affect this. | en_US |
