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Role of T cell receptors in suppressing HIV infection in elite controllers

Joglekar, Alok and Lamothe, Pedro A. and Ouyang, Yong and Liu, Zhe and Walker, Bruce D. and Baltimore, David (2016) Role of T cell receptors in suppressing HIV infection in elite controllers. Journal of Immunology, 196 (S1). Art. No. 79.10. ISSN 0022-1767. http://resolver.caltech.edu/CaltechAUTHORS:20160825-140558554

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Abstract

Virtually all HIV-infected patients progress to AIDS if not treated. A group of patients, called Elite Controllers (ECs), can suppress HIV infection without treatment. This ability of ECs is, in part, due to potent CD8+ T cell (CTL) responses against HIV epitopes presented by human leukocyte antigen (HLA) molecules. In this study, we focused on CTL responses restricted to HLA-B27, an allele that is enriched in ECs, but is not sufficient for protective ability. In HLA-B27+ ECs or non-controllers (NCs), immunodominant CTL responses specific to the KK10 epitope in Gag are found. Previous studies have shown that unlike NCs, B27-KK10-specific CTLs from ECs are efficient at eliminating HIV-infected or KK10-peptide pulsed cells. As the potency of CTLs can be modulated by their T cell receptor (TCR), we hypothesized that B27-KK10-specific TCRs play a significant role in suppressing HIV in ECs. Therefore, we cloned B27-KK10-specific TCRs from ECs or NCs, expressed them in primary T cells, and tested their cytotoxicity. We incubated TCR-transduced T cells with either HIV-infected or KK10-peptide pulsed target cells and measured target cell lysis. Unexpectedly, EC-TCRs were not significantly different than NC-TCRs in their cytotoxicity. We then tested the ability of these cells to suppress HIV in humanized mice and found no significant difference between EC- and NC-TCRs. We are currently investigating various aspects of these TCRs such as cross-reactivity to variants of KK10. The result that TCRs from ECs and non-controllers do not recapitulate the phenotype of CTLs is intriguing and warrants further studies to uncover the mechanism of immunologic control of HIV. Our studies also have implications in immunotherapy and vaccine approaches for HIV.


Item Type:Article
Related URLs:
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http://www.jimmunol.org/content/196/1_Supplement/79.10.shortPublisherArticle
ORCID:
AuthorORCID
Baltimore, David0000-0001-8723-8190
Additional Information:© 2016 The American Association of Immunologists, Inc.
Record Number:CaltechAUTHORS:20160825-140558554
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:20160825-140558554
Official Citation:Role of T cell receptors in suppressing HIV infection in elite controllers Alok Joglekar, Pedro A Lamothe, Yong Ouyang, Zhe Liu, Bruce D Walker, and David Baltimore J Immunol 2016 196:79.10
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:69948
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:26 Aug 2016 15:42
Last Modified:26 Aug 2016 15:42

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