Chen, Huabiao and Ndhlovu, Zaza M. and Liu, Dongfang and Porter, Lindsay C. and Fang, Justin W. and Darko, Sam and Brockman, Mark A. and Miura, Toshiyuki and Brumme, Zabrina L. and Schneidewind, Arne and Piechocka-Trocha, Alicja and Cesa, Kevin T. and Sela, Jennifer and Cung, Thai D. and Toth, Ildiko and Pereyra, Florencia and Yu, Xu G. and Douek, Daniel C. and Kaufmann, Daniel E. and Allen, Todd M. and Walker, Bruce D. (2012) TCR clonotypes modulate the protective effect of HLA class I molecules in HIV-1 infection. NATURE IMMUNOLOGY, 13 (7). 691-+. ISSN 1529-2908,
Full text not available from this repository. (Request a copy)Abstract
The human leukocyte antigens HLA-B*27 and HLA-B*57 are associated with protection against progression of disease that results from infection with human immunodeficiency virus type 1 (HIV-1), yet most people with alleles encoding HLA-B*27 and HLA-B*57 are unable to control HIV-1. Here we found that HLA-B*27-restricted CD8(+) T cells in people able to control infection with HIV-1 (controllers) and those who progress to disease after infection with HIV-1 (progressors) differed in their ability to inhibit viral replication through targeting of the immunodominant epitope of group-associated antigen (Gag) of HIV-1. This was associated with distinct T cell antigen receptor (TCR) clonotypes, characterized by superior control of HIV-1 replication in vitro, greater cross-reactivity to epitope variants and enhanced loading and delivery of perforin. We also observed clonotype-specific differences in antiviral efficacy for an immunodominant HLA-B*57-restricted response in controllers and progressors. Thus, the efficacy of such so-called 'protective alleles' is modulated by specific TCR clonotypes selected during natural infection, which provides a functional explanation for divergent HIV-1 outcomes.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | IMMUNODEFICIENCY-VIRUS TYPE-1; CD8(+) T-CELLS; VIRAL LOAD; ELITE CONTROLLERS; REPLICATION CAPACITY; DISEASE PROGRESSION; LYMPHOCYTE ESCAPE; IMMUNE CONTROL; RESPONSES; EPITOPE; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin I |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 11 May 2020 09:08 |
| Last Modified: | 11 May 2020 09:08 |
| URI: | https://pred.uni-regensburg.de/id/eprint/18541 |
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