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The HIV-1 HLA-A2-SLYNTVATL Is a Help-Independent CTL Epitope
| Content Provider | Scilit |
|---|---|
| Author | Kan-Mitchell, June Bisikirska, Brygida Wong-Staal, Flossie Schaubert, Keri L. Bajcz, Melissa Bereta, Michal |
| Copyright Year | 2004 |
| Description | The CTL response to the HLA-A*0201-restricted, HIV-1 p17 $Gag_{77–85}$ epitope (SLYNTVATL; SL9) has been extensively studied in patients. Although this reactivity is exceptionally prominent in chronically infected patients and inversely correlated to viral load, SL9-specific CTLs (SL9-CTLs) are rarely detected in acute infection. To explore the cellular basis for this unusual manifestation, SL9-CTLs primed ex vivo from naive circulating $CD8^{+}$ T cells of healthy, seronegative donors were generated and characterized. SL9 appeared to differ from other well-studied A*0201-restricted epitopes in several significant respects. In contrast to published reports for influenza and melanoma peptides and the HIV gag IV9 epitope studied here in parallel, SL9-CTLs were primed by immature but not mature autologous dendritic cells. Highly activated SL9-CTLs produce sufficient autocrine mediators to sustain clonal expansion and CTL differentiation for months without $CD4^{+}$ T cells or exogenous IL-2. Moreover, SL9-CTLs were sensitive to paracrine IL-2-induced apoptosis. IL-2 independence and sensitivity to paracrine IL-2 were also characteristic of SL9-CTLs immunized by dendritic cells transduced by a nonreplicating lentiviral vector encoding full-length Gag. In vitro-primed SL9-CTLs resembled those derived from patients in degeneracy of recognition and functional avidities for both SL9 and its natural mutations. Together, these data show that SL9 is a highly immunogenic, help-independent HIV epitope. The scarcity of SL9-CTLs in acute infection may result from cytokine-induced apoptosis with the intense activation of the innate immunity. In contrast, SL9-CTLs that constitutively produce autocrine help would predominate during CD4-diminished chronic infection. |
| Ending Page | 5261 |
| Page Count | 13 |
| Starting Page | 5249 |
| ISSN | 00221767 |
| e-ISSN | 15506606 |
| DOI | 10.4049/jimmunol.172.9.5249 |
| Journal | The Journal of Immunology |
| Issue Number | 9 |
| Volume Number | 172 |
| Language | English |
| Publisher | The American Association of Immunologists |
| Publisher Date | 2004-05-01 |
| Access Restriction | Open |
| Subject Keyword | Viral Load Lentiviral Vector Innate Immunity Acute Infection |
| Content Type | Text |
| Resource Type | Article |
| Subject | Immunology and Allergy Immunology |
