20980521
not annotated - annotated - LINNAEUS only
Characterization of cross-reactive CD8+ T-cell recognition of HLA-A2-restricted HIV-Gag (SLYNTVATL) and HCV-NS5b (ALYDVVSKL) epitopes in individuals infected with human immunodeficiency and hepatitis C viruses.
The immunologic mechanisms underlying the faster progression of hepatitis C virus (HCV) disease in the presence of human immunodeficiency virus (HIV) coinfection are not clearly understood. T-cell cross-reactivity between HCV and influenza virus-specific epitopes has been associated with rapid progression of HCV disease (S. Urbani, B. Amadei, P. Fisicaro, M. Pilli, G. Missale, A. Bertoletti, and C. Ferrari, J. Exp. Med. 201:675-680, 2005). We asked whether T-cell cross-reactivity between HCV and HIV could exist during HCV/HIV coinfection and affect pathogenesis. Our search for amino acid sequence homology between the HCV and HIV proteomes revealed two similar HLA-A2-restricted epitopes, HIV-Gag (SLYNTVATL [HIV-SL9]) and HCV-NS5b (ALYDVVSKL [HCV-AL9]). We found that 4 out of 20 HLA-A2-positive (HLA-A2(+)) HIV-infected individuals had CD8(+) T cells that recognized both the HIV-SL9 and HCV-AL9 epitopes. However, the AL9 epitope was generally shown to be a weak agonist. Although HCV-monoinfected individuals in our study did not show AL9-specific responses, we found that about half of HCV/HIV-coinfected individuals had dual responses to both epitopes. High dual T-cell recognition among coinfected subjects was usually due to separate T-cell populations targeting each epitope, as determined by pentamer staining. The one individual demonstrating cross-reactive T cells to both epitopes showed the most advanced degree of liver disease. In coinfected individuals, we observed a positive correlation between the magnitudes of T-cell responses to both the SL9 and the AL9 epitopes, which was also positively associated with the clinical parameter of liver damage. Thus, we find that HIV infection induces T cells that can cross-react to heterologous viruses or prime for T cells that are closely related in sequence. However, the induction of cross-reactive T cells may not be associated with control of disease caused by the heterologous virus. This demonstrates that degeneracy of HIV-specific T cells may play a role in the immunopathology of HCV/HIV coinfection.
Ann file
T1 Species 163 185;202 209 human immunodeficiency viruses
N1 Reference T1 Taxonomy:12721
T2 Species 190 209 hepatitis C viruses
N2 Reference T2 Taxonomy:11103
T3 Species 296 299 HCV
N3 Reference T3 Taxonomy:11103
T4 Species 328 356 human immunodeficiency virus
N4 Reference T4 Taxonomy:12721
T5 Species 358 361 HIV
N5 Reference T5 Taxonomy:12721
T6 Species 435 438 HCV
N6 Reference T6 Taxonomy:11103
T7 Species 523 526 HCV
N7 Reference T7 Taxonomy:11103
T8 Species 714 717 HIV
N8 Reference T8 Taxonomy:12721
T9 Species 737 740 HCV
N9 Reference T9 Taxonomy:11103
T10 Species 741 744 HIV
T11 Species 846 849 HIV
N11 Reference T11 Taxonomy:12721
T12 Species 943 946 HCV
N12 Reference T12 Taxonomy:11103
T13 Species 964 967 HCV
N13 Reference T13 Taxonomy:11103
T14 Species 1029 1032 HIV
N14 Reference T14 Taxonomy:12721
T15 Species 1098 1101 HIV
N15 Reference T15 Taxonomy:12721
T16 Species 1315 1318 HIV
N16 Reference T16 Taxonomy:12721
T17 Species 2271 2274 HCV
N17 Reference T17 Taxonomy:11103
T18 Species 2275 2278 HIV
N18 Reference T18 Taxonomy:12721
T19 Species 277 294 hepatitis C virus
N19 Reference T19 Taxonomy:11103
T20 Species 104 107 HCV
N20 Reference T20 Taxonomy:11103
N10 Reference T10 Taxonomy:12721
T21 Species 80 83 HIV
N21 Reference T21 Taxonomy:12721
T22 Species 1204 1207 HCV
N22 Reference T22 Taxonomy:11103
T23 Species 443 458 influenza virus
N23 Reference T23 Taxonomy:11320 Influenza A virus
T24 Species 706 709 HCV
N24 Reference T24 Taxonomy:11103
T25 Species 838 841 HCV
N25 Reference T25 Taxonomy:11103
T26 Species 1311 1314 HCV
N26 Reference T26 Taxonomy:11103
T27 Species 1908 1911 HIV
N27 Reference T27 Taxonomy:12721
T28 Species 2208 2211 HIV
N28 Reference T28 Taxonomy:12721
T29 Species 1110 1113 HCV
N29 Reference T29 Taxonomy:11103
T30 Species 909 912 HIV
N30 Reference T30 Taxonomy:12721