Spreading of HIV-specific CD8+ T-cell repertoire in long-term nonprogressors and its role in the control of viral load and disease activity

Propato, Antonella; Schiaffella, Enrico; Vicenzi, Elisa; Francavilla, Vittorio; Baloni, Letizia; Paroli, Marino; Finocchi, Luigi; Tanigaki, Nobuyuki; Ghezzi, Silvia; Ferrara, Rosa; Chesnut, Robert W.; Livingston, Brian; Sette, Alessandro; Paganelli, Roberto; Aiuti, F; Poli, Guido; Barnaba, Vincenzo

doi:10.1016/s0198-8859(01)00245-2

Cited by 52 publications

(39 citation statements)

References 45 publications

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“…Whereas the correlation between B44 and the E35D mutation was highly significant (P ϭ 1.2 ϫ 10 9 ), B44 correlated only weakly with P39S (P ϭ 0.048) ( Table 2). Another association was identified between M46L/I (P ϭ 0.049), a major drug mutation (15) located in the previously described A2-restricted epitope KM IGGIGGFI (KI10; PR amino acids 45 to 54) (30), and HLA-A2. HLA-A11 was associated with I13V (P ϭ 0.012), a minor tipranavir resistance mutation (15) located in the previously described A11-restricted epitope VTIKIGGQLK (amino acids 11 to 20) (24) ( Table 2).…”

Section: Resultsmentioning

confidence: 93%

“…For the further assessment of the influence of CD8 ϩ T cells on the development of resistance mutations, we focused on the B44-restricted epitope EW9 (EEMNLPGRW; PR amino acids 34 to 42) (33) and the A2-restricted epitope KI10 (KMIGGI GGFI; PR amino acids 45 to 54) (30). In our patient cohort, we observed a number of mutations in the EW9 epitope, indicating strong selection pressure by CD8 ϩ T cells.…”

Section: Discussionmentioning

confidence: 98%

“…In contrast to EW9, the HLA-A2-restricted epitope KMIGGIGGFI (KI10; PR amino acids 45 to 54) (30), containing the drug resistance mutations M46I/L and I54V, is rather conserved. Cells from roughly 35% of the A2-positive patients showed CD8…”

Section: Variations In the B44-restricted Ew9 Epitope Can Influence Rmentioning

confidence: 99%

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Dual Selection Pressure by Drugs and HLA Class I-Restricted Immune Responses on Human Immunodeficiency Virus Type 1 Protease

Mueller

Schaetz

Eismann

et al. 2007

J Virol

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Section: Resultsmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 98%

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Dual Selection Pressure by Drugs and HLA Class I-Restricted Immune Responses on Human Immunodeficiency Virus Type 1 Protease

Mueller

Schaetz

Eismann

et al. 2007

J Virol

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“…Sette et al (16) found that by focusing only on the HLA class I A1, A2, A3, A24, and B7 supertypes, 100% population coverage is achieved (76). The strategy of epitope selection based on HLA supertypes has been validated in different disease settings worldwide (77)(78)(79)(80)(81)(82). However, while HLA class I supertypes have been widely explored, class II supertypes are still in the relatively early stages of investigation.…”

Section: Discussionmentioning

confidence: 99%

In Silico Identification of Supertypes for Class II MHCs

Doytchinova

Flower

2005

The Journal of Immunology

177

192

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The development of epitope-based vaccines, which have wide population coverage, is greatly complicated by MHC polymorphism. The grouping of alleles into supertypes, on the basis of common structural and functional features, addresses this problem directly. In the present study we applied a combined bioinformatics approach, based on analysis of both protein sequence and structure, to identify similarities in the peptide binding sites of 2225 human class II MHC molecules, and thus define supertypes and supertype fingerprints. Two chemometric techniques were used: hierarchical clustering using three-dimensional Comparative Similarity Indices Analysis fields and nonhierarchical k-means clustering using sequence-based z-descriptors. An average consensus of 84% was achieved, i.e., 1872 of 2225 class II molecules were classified in the same supertype by both techniques. Twelve class II supertypes were defined: five DRs, three DQs, and four DPs. The HLA class II supertypes and their fingerprints given in parenthesis are DR1 (Trp9β), DR3 (Glu9β, Gln70β, and Gln/Arg74β), DR4 (Glu9β, Gln/Arg70β, and Glu/Ala74β), DR5 (Glu9β, Asp70β), and DR9 (Lys/Gln9β); DQ1 (Ala/Gly86β), DQ2 (Glu86β, Lys71β), and DQ3 (Glu86β, Thr/Asp71β); DPw1 (Asp84β and Lys69β), DPw2 (Gly/Val84β and Glu69β), DPw4 (Gly/Val84β and Lys69β), and DPw6 (Asp84β and Glu69β). Apart from the good agreement between known binding motifs and our classification, several new supertypes, and corresponding thematic binding motifs, were also defined.

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“…CTL responses to SL9 are exceptionally prominent in chronically infected patients but rarely detected in acute infection, and SL9-specific CTL are inversely correlated to viral load in HIV patients (21)(22)(23)(24). The HIV-1 integrase epitope MA10 is a major CD8 T cell epitope recognized by resting memory T cells of long-term nonprogressors (25).…”

Section: Discussionmentioning

confidence: 99%

Induction of primary anti-HIV CD4 and CD8 T cell responses by dendritic cells transduced with self-inactivating lentiviral vectors

Chen¹,

Wang²,

Chang³

2006

Cellular Immunology

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In this study, we demonstrate that a minimal self-inactivating (SIN) lentiviral vector (LV) that does not encode any human immunodeficiency virus (HIV) genes is able to induce autologous HIVspecific CD4 and CD8 T cell responses after transduction of dendritic cells (DCs). The LV-DCprimed T cells displayed HIV-specific lytic degranulation, as illustrated by acquisition of CD107a/ b expression on the cell surface and release of perforin. HIV-specific cytotoxic T lymphocyte (CTL) response was consistently detected using different assays, and T cell receptors specific to three prominent HIV epitopes, SL9 (Gag peptide: SLYNTVATL), IV9 (Pol peptide: ILKEPVHGV), and MA10 (In Peptide: MASDFNLPPV) were detected using HLA-A0201 peptide-tetramers. These results demonstrate that DCs transduced with the minimal SIN-LV can efficiently induce HIVspecific CD4 and CD8 T cell responses. Since LVs are popular gene transfer tools, our results have fundamental implications for future LV applications and DC vaccine development.

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Spreading of HIV-specific CD8+ T-cell repertoire in long-term nonprogressors and its role in the control of viral load and disease activity

Cited by 52 publications

References 45 publications

Dual Selection Pressure by Drugs and HLA Class I-Restricted Immune Responses on Human Immunodeficiency Virus Type 1 Protease

Dual Selection Pressure by Drugs and HLA Class I-Restricted Immune Responses on Human Immunodeficiency Virus Type 1 Protease

In Silico Identification of Supertypes for Class II MHCs

Induction of primary anti-HIV CD4 and CD8 T cell responses by dendritic cells transduced with self-inactivating lentiviral vectors

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