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- Epitopes that have undergone escape are often still immunogenic. Scanning for epitopes that encompass HLA-specific polymorphisms revealed 97 HLA-polymorphism associations in which the mutation resulted in the creation rather than abolition of an epitope, termed a "neo-epitope". This study examined 9 neo-epitopes that were well-characterized optimal epitopes that elicit T-cell responses in chronic infection. HIV-1 adaptation not only abrogates the immune recognition of early targeted epitopes, but may also increase immune recognition to other epitopes, which elicit immunodominant but non-protective T-cell responses.
- Neo-epitope KRQEILDWVY underwent adaptation from KRQDILDWVY. 8 subjects had higher EliSpot responses to the neo-epitope than to the non-adapted form.
- HLA-C*0702-expressing PBMCs from 7 individuals were cultured with KY11 adapted and non-adapted epitopes to generate epitope-specific T-cell lines. The frequencies of central memory and effector memory T cells were not significantly different whether directed against non-adapted or adapted epitopes.
- In chromium release assays, B-cell targets pulsed with non-adapted KY11 were killed more readily by non-adapted KY11 T cells, compared to those pulsed with the adapted form. However, the reverse was observed for T cells, which killed fewer adapted KY11-pulsed targets compared with non-adapted.
- No difference was found in TCR expression between epitope-specific CTLs from adapted and non-adapted forms of this epitope.
Niamh M. Keane, Steven G. Roberts, Coral-Ann M. Almeida, Tanya Krishnan, Abha Chopra, Emma Demaine, Rebecca Laird, Monika Tschochner, Jonathan M. Carlson, Simon Mallal, David Heckerman, Ian James, and Mina John. High-Avidity, High-IFN-gamma-Producing CD8 T-Cell Responses following Immune Selection during HIV-1 Infection. Immunol. Cell Biol., 90(2):224-234, Feb 2012. PubMed ID: 21577229.
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