HLA-B*14: 02-restricted Env-specific CD8+ T-cell activity has highly potent antiviral efficacy associated with immune control of HIV infection

Ellen M. Leitman; Christian B. Willberg; Ming Han Tsai; Huabiao Chen; Søren Buus; Fabian Chen; Lynn Riddell; David Haas; Jacques Fellay; James J. Goedert; Alicja Piechocka-Trocha; Bruce D. Walker; Jeffrey Martin; Steven Deeks; Steven M. Wolinsky; Jeremy Martinson; Maureen Martin; Ying Qi; Asier Sáez-Cirión; Otto O. Yang; Philippa C. Matthews; Mary Carrington; Philip J.R. Goulder

doi:10.1128/JVI.00544-17

HLA-B*14: 02-restricted Env-specific CD8⁺ T-cell activity has highly potent antiviral efficacy associated with immune control of HIV infection

Ellen M. Leitman^*, Christian B. Willberg, Ming Han Tsai, Huabiao Chen, Søren Buus, Fabian Chen, Lynn Riddell, David Haas, Jacques Fellay, James J. Goedert, Alicja Piechocka-Trocha, Bruce D. Walker, Jeffrey Martin, Steven Deeks, Steven M. Wolinsky, Jeremy Martinson, Maureen Martin, Ying Qi, Asier Sáez-Cirión, Otto O. YangPhilippa C. Matthews, Mary Carrington, Philip J.R. Goulder

^*Corresponding author for this work

8 Citations (Scopus)

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Abstract

Immune control of human immunodeficiency virus type 1 (HIV) infection is typically associated with effective Gag-specific CD8⁺ T-cell responses. We here focus on HLA-B*14, which protects against HIV disease progression, but the immunodominant HLA-B*14-restricted anti-HIV response is Env specific (ERYLKDQQL, HLA-B*14-EL9). A subdominant HLA-B*14-restricted response targets Gag (DRYFKTLRA, HLA-B*14-DA9). Using HLA-B*14/peptide-saporin-conjugated tetramers, we show that HLA-B*14-EL9 is substantially more potent at inhibiting viral replication than HLA-B*14-DA9. HLA-B*14-EL9 also has significantly higher functional avidity (P < 0.0001) and drives stronger selection pressure on the virus than HLA-B*14-DA9. However, these differences were HLA-B*14 subtype specific, applying only to HLA-B*14:02 and not to HLA-B*14:01. Furthermore, the HLA-B*14-associated protection against HIV disease progression is significantly greater for HLA-B*14:02 than for HLA-B*14:01, consistent with the superior antiviral efficacy of the HLA-B*14-EL9 response. Thus, although Gag-specific CD8⁺ T-cell responses may usually have greater anti-HIV efficacy, factors independent of protein specificity, including functional avidity of individual responses, are also critically important to immune control of HIV.

Original language	English
Article number	e00544-17
Journal	Journal of Virology
Volume	91
Issue number	22
Number of pages	19
ISSN	0022-538X
DOIs	https://doi.org/10.1128/JVI.00544-17
Publication status	Published - Nov 2017

Keywords

CD8 T cells
HIV
HLA-B*14
Immune control

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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Cite this

Leitman, E. M., Willberg, C. B., Tsai, M. H., Chen, H., Buus, S., Chen, F., Riddell, L., Haas, D., Fellay, J., Goedert, J. J., Piechocka-Trocha, A., Walker, B. D., Martin, J., Deeks, S., Wolinsky, S. M., Martinson, J., Martin, M., Qi, Y., Sáez-Cirión, A., ... Goulder, P. J. R. (2017). HLA-B*14: 02-restricted Env-specific CD8⁺ T-cell activity has highly potent antiviral efficacy associated with immune control of HIV infection. Journal of Virology, 91(22), [e00544-17]. https://doi.org/10.1128/JVI.00544-17

Leitman, EM, Willberg, CB, Tsai, MH, Chen, H, Buus, S, Chen, F, Riddell, L, Haas, D, Fellay, J, Goedert, JJ, Piechocka-Trocha, A, Walker, BD, Martin, J, Deeks, S, Wolinsky, SM, Martinson, J, Martin, M, Qi, Y, Sáez-Cirión, A, Yang, OO, Matthews, PC, Carrington, M & Goulder, PJR 2017, 'HLA-B*14: 02-restricted Env-specific CD8⁺ T-cell activity has highly potent antiviral efficacy associated with immune control of HIV infection', Journal of Virology, vol. 91, no. 22, e00544-17. https://doi.org/10.1128/JVI.00544-17

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title = "HLA-B*14: 02-restricted Env-specific CD8+ T-cell activity has highly potent antiviral efficacy associated with immune control of HIV infection",

abstract = "Immune control of human immunodeficiency virus type 1 (HIV) infection is typically associated with effective Gag-specific CD8+ T-cell responses. We here focus on HLA-B*14, which protects against HIV disease progression, but the immunodominant HLA-B*14-restricted anti-HIV response is Env specific (ERYLKDQQL, HLA-B*14-EL9). A subdominant HLA-B*14-restricted response targets Gag (DRYFKTLRA, HLA-B*14-DA9). Using HLA-B*14/peptide-saporin-conjugated tetramers, we show that HLA-B*14-EL9 is substantially more potent at inhibiting viral replication than HLA-B*14-DA9. HLA-B*14-EL9 also has significantly higher functional avidity (P < 0.0001) and drives stronger selection pressure on the virus than HLA-B*14-DA9. However, these differences were HLA-B*14 subtype specific, applying only to HLA-B*14:02 and not to HLA-B*14:01. Furthermore, the HLA-B*14-associated protection against HIV disease progression is significantly greater for HLA-B*14:02 than for HLA-B*14:01, consistent with the superior antiviral efficacy of the HLA-B*14-EL9 response. Thus, although Gag-specific CD8+ T-cell responses may usually have greater anti-HIV efficacy, factors independent of protein specificity, including functional avidity of individual responses, are also critically important to immune control of HIV.",

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T2 - 02-restricted Env-specific CD8+ T-cell activity has highly potent antiviral efficacy associated with immune control of HIV infection

AU - Leitman, Ellen M.

AU - Willberg, Christian B.

AU - Tsai, Ming Han

AU - Chen, Huabiao

AU - Buus, Søren

AU - Chen, Fabian

AU - Riddell, Lynn

AU - Haas, David

AU - Fellay, Jacques

AU - Goedert, James J.

AU - Piechocka-Trocha, Alicja

AU - Walker, Bruce D.

AU - Martin, Jeffrey

AU - Deeks, Steven

AU - Wolinsky, Steven M.

AU - Martinson, Jeremy

AU - Martin, Maureen

AU - Qi, Ying

AU - Sáez-Cirión, Asier

AU - Yang, Otto O.

AU - Matthews, Philippa C.

AU - Carrington, Mary

AU - Goulder, Philip J.R.

PY - 2017/11

Y1 - 2017/11

N2 - Immune control of human immunodeficiency virus type 1 (HIV) infection is typically associated with effective Gag-specific CD8+ T-cell responses. We here focus on HLA-B*14, which protects against HIV disease progression, but the immunodominant HLA-B*14-restricted anti-HIV response is Env specific (ERYLKDQQL, HLA-B*14-EL9). A subdominant HLA-B*14-restricted response targets Gag (DRYFKTLRA, HLA-B*14-DA9). Using HLA-B*14/peptide-saporin-conjugated tetramers, we show that HLA-B*14-EL9 is substantially more potent at inhibiting viral replication than HLA-B*14-DA9. HLA-B*14-EL9 also has significantly higher functional avidity (P < 0.0001) and drives stronger selection pressure on the virus than HLA-B*14-DA9. However, these differences were HLA-B*14 subtype specific, applying only to HLA-B*14:02 and not to HLA-B*14:01. Furthermore, the HLA-B*14-associated protection against HIV disease progression is significantly greater for HLA-B*14:02 than for HLA-B*14:01, consistent with the superior antiviral efficacy of the HLA-B*14-EL9 response. Thus, although Gag-specific CD8+ T-cell responses may usually have greater anti-HIV efficacy, factors independent of protein specificity, including functional avidity of individual responses, are also critically important to immune control of HIV.

AB - Immune control of human immunodeficiency virus type 1 (HIV) infection is typically associated with effective Gag-specific CD8+ T-cell responses. We here focus on HLA-B*14, which protects against HIV disease progression, but the immunodominant HLA-B*14-restricted anti-HIV response is Env specific (ERYLKDQQL, HLA-B*14-EL9). A subdominant HLA-B*14-restricted response targets Gag (DRYFKTLRA, HLA-B*14-DA9). Using HLA-B*14/peptide-saporin-conjugated tetramers, we show that HLA-B*14-EL9 is substantially more potent at inhibiting viral replication than HLA-B*14-DA9. HLA-B*14-EL9 also has significantly higher functional avidity (P < 0.0001) and drives stronger selection pressure on the virus than HLA-B*14-DA9. However, these differences were HLA-B*14 subtype specific, applying only to HLA-B*14:02 and not to HLA-B*14:01. Furthermore, the HLA-B*14-associated protection against HIV disease progression is significantly greater for HLA-B*14:02 than for HLA-B*14:01, consistent with the superior antiviral efficacy of the HLA-B*14-EL9 response. Thus, although Gag-specific CD8+ T-cell responses may usually have greater anti-HIV efficacy, factors independent of protein specificity, including functional avidity of individual responses, are also critically important to immune control of HIV.

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KW - HIV

KW - HLA-B14

KW - Immune control

U2 - 10.1128/JVI.00544-17

DO - 10.1128/JVI.00544-17

M3 - Journal article

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AN - SCOPUS:85032297543

SN - 0022-538X

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JO - Journal of Virology

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