Differential immunodominance hierarchy of CD8+ T-cell responses in HLA-B*27: 05- and -B*27:02-mediated control of HIV-1 infection
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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Differential immunodominance hierarchy of CD8+ T-cell responses in HLA-B*27 : 05- and -B*27:02-mediated control of HIV-1 infection. / Adland, Emily; Hill, Matilda; Lavandier, Nora; Csala, Anna; Edwards, Anne; Chen, Fabian; Radkowski, Marek; Kowalska, Justyna D.; Paraskevis, Dimitrios; Hatzakis, Angelos; Valenzuela-Ponce, Humberto; Pfafferott, Katja; Williams, Ian; Pellegrino, Pierre; Borrow, Persephone; Mori, Masahiko; Rockstroh, Jürgen; Prado, Julia G.; Mothe, Beatriz; Dalmau, Judith; Martinez-Picado, Javier; Tudor-Williams, Gareth; Frater, John; Stryhn, Anette; Buus, Soren; Teran, Gustavo Reyes; Mallal, Simon; John, Mina; Buchbinder, Susan; Kirk, Gregory; Martin, Jeffrey; Michael, Nelson; Fellay, Jacques; Deeks, Steve; Walker, Bruce; Avila-Rios, Santiago; Cole, David; Brander, Christian; Carrington, Mary; Goulder, Philip.
I: Journal of Virology, Bind 92, Nr. 4, e01685-17, 02.2018.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Differential immunodominance hierarchy of CD8+ T-cell responses in HLA-B*27
T2 - 05- and -B*27:02-mediated control of HIV-1 infection
AU - Adland, Emily
AU - Hill, Matilda
AU - Lavandier, Nora
AU - Csala, Anna
AU - Edwards, Anne
AU - Chen, Fabian
AU - Radkowski, Marek
AU - Kowalska, Justyna D.
AU - Paraskevis, Dimitrios
AU - Hatzakis, Angelos
AU - Valenzuela-Ponce, Humberto
AU - Pfafferott, Katja
AU - Williams, Ian
AU - Pellegrino, Pierre
AU - Borrow, Persephone
AU - Mori, Masahiko
AU - Rockstroh, Jürgen
AU - Prado, Julia G.
AU - Mothe, Beatriz
AU - Dalmau, Judith
AU - Martinez-Picado, Javier
AU - Tudor-Williams, Gareth
AU - Frater, John
AU - Stryhn, Anette
AU - Buus, Soren
AU - Teran, Gustavo Reyes
AU - Mallal, Simon
AU - John, Mina
AU - Buchbinder, Susan
AU - Kirk, Gregory
AU - Martin, Jeffrey
AU - Michael, Nelson
AU - Fellay, Jacques
AU - Deeks, Steve
AU - Walker, Bruce
AU - Avila-Rios, Santiago
AU - Cole, David
AU - Brander, Christian
AU - Carrington, Mary
AU - Goulder, Philip
PY - 2018/2
Y1 - 2018/2
N2 - The well-characterized association between HLA-B*27:05 and protection against HIV disease progression has been linked to immunodominant HLA-B*27:05- restricted CD8+ T-cell responses toward the conserved Gag KK10 (residues 263 to 272) and polymerase (Pol) KY9 (residues 901 to 909) epitopes. We studied the impact of the 3 amino acid differences between HLA-B*27:05 and the closely related HLA-B*27:02 on the HIV-specific CD8+ T-cell response hierarchy and on immune control of HIV. Genetic epidemiological data indicate that both HLA-B*27:02 and HLA-B*27:05 are associated with slower disease progression and lower viral loads. The effect of HLA-B*27:02 appeared to be consistently stronger than that of HLAB* 27:05. In contrast to HLA-B*27:05, the immunodominant HIV-specific HLA-B*27:02- restricted CD8+ T-cell response is to a Nef epitope (residues 142 to 150 [VW9]), with Pol KY9 subdominant and Gag KK10 further subdominant. This selection was driven by structural differences in the F pocket, mediated by a polymorphism between these two HLA alleles at position 81. Analysis of autologous virus sequences showed that in HLA-B*27:02-positive subjects, all three of these CD8+ T-cell responses impose selection pressure on the virus, whereas in HLA-B*27:05-positive subjects, there is no Nef VW9-mediated selection pressure. These studies demonstrate that HLAB* 27:02 mediates protection against HIV disease progression that is at least as strong as or stronger than that mediated by HLA-B*27:05. In combination with the protective Gag KK10 and Pol KY9 CD8+ T-cell responses that dominate HIV-specific CD8+ T-cell activity in HLA-B*27:05-positive subjects, a Nef VW9-specific response is additionally present and immunodominant in HLA-B*27:02-positive subjects, mediated through a polymorphism at residue 81 in the F pocket, that contributes to selection pressure against HIV.
AB - The well-characterized association between HLA-B*27:05 and protection against HIV disease progression has been linked to immunodominant HLA-B*27:05- restricted CD8+ T-cell responses toward the conserved Gag KK10 (residues 263 to 272) and polymerase (Pol) KY9 (residues 901 to 909) epitopes. We studied the impact of the 3 amino acid differences between HLA-B*27:05 and the closely related HLA-B*27:02 on the HIV-specific CD8+ T-cell response hierarchy and on immune control of HIV. Genetic epidemiological data indicate that both HLA-B*27:02 and HLA-B*27:05 are associated with slower disease progression and lower viral loads. The effect of HLA-B*27:02 appeared to be consistently stronger than that of HLAB* 27:05. In contrast to HLA-B*27:05, the immunodominant HIV-specific HLA-B*27:02- restricted CD8+ T-cell response is to a Nef epitope (residues 142 to 150 [VW9]), with Pol KY9 subdominant and Gag KK10 further subdominant. This selection was driven by structural differences in the F pocket, mediated by a polymorphism between these two HLA alleles at position 81. Analysis of autologous virus sequences showed that in HLA-B*27:02-positive subjects, all three of these CD8+ T-cell responses impose selection pressure on the virus, whereas in HLA-B*27:05-positive subjects, there is no Nef VW9-mediated selection pressure. These studies demonstrate that HLAB* 27:02 mediates protection against HIV disease progression that is at least as strong as or stronger than that mediated by HLA-B*27:05. In combination with the protective Gag KK10 and Pol KY9 CD8+ T-cell responses that dominate HIV-specific CD8+ T-cell activity in HLA-B*27:05-positive subjects, a Nef VW9-specific response is additionally present and immunodominant in HLA-B*27:02-positive subjects, mediated through a polymorphism at residue 81 in the F pocket, that contributes to selection pressure against HIV.
KW - CD8 T cell
KW - HIV Gag
KW - HIV Nef
KW - HLA
KW - HLA-B27
KW - Human immunodeficiency virus
U2 - 10.1128/JVI.01685-17
DO - 10.1128/JVI.01685-17
M3 - Journal article
C2 - 29167337
AN - SCOPUS:85041231839
VL - 92
JO - Journal of Virology
JF - Journal of Virology
SN - 0022-538X
IS - 4
M1 - e01685-17
ER -
ID: 189625682