Abstract
Background: CD4+ T cells orchestrate immune protection by
‘‘helping’’ other cells of our immune system to clear viral infections.
It is well known that the preferential infection and depletion of
CD4+ T cells contributes to hampered systemic T cell help following
HIV infection. However, the functional and immunodominant
discrepancies of CD4+ T cell responses targeting promiscuous
MHC II restricted HIV epitopes remains poorly defined. Thus, utilization
of interdisciplinary approaches might aid revealing broadly-
reactive peptides eliciting CD4 + T cell responses.
Methods: We utilized the novel bioinformatic prediction program
NetMHCIIpan to select 64 optimized MHC II restricted
epitopes located in the HIV Gag, Pol, Env, Nef and Tat regions.
The epitopes were selected to cover the global diversity of the
virus (multiple subtypes) and the human immune system(diverse
MHC II types). Optimized polychromatic flow cytometry analysis,
including the functional markers IFNc, IL-2, IL-21, MIP-Ib and
TNFa, revealed immunogenicity of the individual epitopes.
The study subjects (n = 38) were of diverse ethnical background
infected by different HIV subtypes. High resolution HLA typing
and sequences of the HIV-Gag and Nef regions were obtained.
Results: The FACS analysis revealed immunogenicity against
73% of the epitopes. All subjects, except one, recognized at least
one epitope. Interestingly, almost all epitopes located in Gag (15/
15) and Nef (14/15) elicited responses, while epitopes in Pol (10/
15) and Env (5/15) revealed restricted CD4 + T cell immunogenicity.
This difference in immunogenicsity between the regions
was significant (One-way ANOVA: p <0.001). Additionally, Gag
and Nef epitopes generated greater polyfunctionality than Poland
Env-specific CD4+ T cells. Importantly, we found that the
use of optimized epitopes improved the polyfunctionality compared
with overlapping HIV Gag (p55) peptides.
Conclusion: Using an unbiased approach where we have predicted
peptides with same prerequisites, we demonstrate that
HIV-specific CD4 + T cell immunodominance is heavily skewed,
targeting particularly Gag and Nef.
Original language | English |
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Journal | AIDS Research and Human Retroviruses |
Volume | 27 |
Issue number | 10 |
Pages (from-to) | A88-A88 |
ISSN | 0889-2229 |
DOIs | |
Publication status | Published - 2011 |
Event | AIDS Vaccine Conference 2011 - Bangkok, Thailand Duration: 12 Sept 2011 → 15 Sept 2011 |
Conference
Conference | AIDS Vaccine Conference 2011 |
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Country/Territory | Thailand |
City | Bangkok |
Period | 12/09/2011 → 15/09/2011 |