HIV-specific cytotoxic T cells from long-term survivors select a unique T cell receptor

T Dong; G Stewart-Jones; N Chen; P Easterbrook; X N Xu; L Papagno; V Appay; M Weekes; C Conlon; C Spina; S Little; G Screaton; A van der Merwe; D D Richman; A J McMichael; E Y Jones; S L Rowland-Jones

doi:10.1084/jem.20032044

HIV-specific cytotoxic T cells from long-term survivors select a unique T cell receptor

T Dong, G Stewart-Jones, N Chen, P Easterbrook, X N Xu, L Papagno, V Appay, M Weekes, C Conlon, C Spina, S Little, G Screaton, A van der Merwe, D D Richman, A J McMichael, E Y Jones, S L Rowland-Jones

King's College London

Research output: Contribution to journal › Article › peer-review

99 Citations (Scopus)

Abstract

HIV-specific cytotoxic T lymphocytes (CTL) are important in controlling HIV replication, but the magnitude of the CTL response does not predict clinical outcome. In four donors with delayed disease progression we identified Vbeta13.2 T cell receptors (TCRs) with very similar and unusually long beta-chain complementarity determining region 3 (CDR3) regions in CTL specific for the immunodominant human histocompatibility leukocyte antigens (HLA)-B8-restricted human immunodeficiency virus-1 (HIV-1) nef epitope, FLKEKGGL (FL8). CTL expressing Vbeta13.2 TCRs tolerate naturally arising viral variants in the FL8 epitope that escape recognition by other CTL. In addition, they expand efficiently in vitro and are resistant to apoptosis, in contrast to FL8-specific CTL using other TCRs. Selection of Vbeta13.2 TCRs by some patients early in the FL8-specific CTL response may be linked with better clinical outcome.

Original language	English
Pages (from-to)	1547 - 1557
Number of pages	11
Journal	Journal of Experimental Medicine
Volume	200
Issue number	12
DOIs	https://doi.org/10.1084/jem.20032044
Publication status	Published - 20 Dec 2004

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Dong, T., Stewart-Jones, G., Chen, N., Easterbrook, P., Xu, X. N., Papagno, L., Appay, V., Weekes, M., Conlon, C., Spina, C., Little, S., Screaton, G., van der Merwe, A., Richman, D. D., McMichael, A. J., Jones, E. Y., & Rowland-Jones, S. L. (2004). HIV-specific cytotoxic T cells from long-term survivors select a unique T cell receptor. Journal of Experimental Medicine, 200(12), 1547 - 1557. https://doi.org/10.1084/jem.20032044

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title = "HIV-specific cytotoxic T cells from long-term survivors select a unique T cell receptor",

abstract = "HIV-specific cytotoxic T lymphocytes (CTL) are important in controlling HIV replication, but the magnitude of the CTL response does not predict clinical outcome. In four donors with delayed disease progression we identified Vbeta13.2 T cell receptors (TCRs) with very similar and unusually long beta-chain complementarity determining region 3 (CDR3) regions in CTL specific for the immunodominant human histocompatibility leukocyte antigens (HLA)-B8-restricted human immunodeficiency virus-1 (HIV-1) nef epitope, FLKEKGGL (FL8). CTL expressing Vbeta13.2 TCRs tolerate naturally arising viral variants in the FL8 epitope that escape recognition by other CTL. In addition, they expand efficiently in vitro and are resistant to apoptosis, in contrast to FL8-specific CTL using other TCRs. Selection of Vbeta13.2 TCRs by some patients early in the FL8-specific CTL response may be linked with better clinical outcome.",

author = "T Dong and G Stewart-Jones and N Chen and P Easterbrook and Xu, {X N} and L Papagno and V Appay and M Weekes and C Conlon and C Spina and S Little and G Screaton and {van der Merwe}, A and Richman, {D D} and McMichael, {A J} and Jones, {E Y} and Rowland-Jones, {S L}",

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doi = "10.1084/jem.20032044",

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Dong, T, Stewart-Jones, G, Chen, N, Easterbrook, P, Xu, XN, Papagno, L, Appay, V, Weekes, M, Conlon, C, Spina, C, Little, S, Screaton, G, van der Merwe, A, Richman, DD, McMichael, AJ, Jones, EY & Rowland-Jones, SL 2004, 'HIV-specific cytotoxic T cells from long-term survivors select a unique T cell receptor', Journal of Experimental Medicine, vol. 200, no. 12, pp. 1547 - 1557. https://doi.org/10.1084/jem.20032044

TY - JOUR

T1 - HIV-specific cytotoxic T cells from long-term survivors select a unique T cell receptor

AU - Dong, T

AU - Stewart-Jones, G

AU - Chen, N

AU - Easterbrook, P

AU - Xu, X N

AU - Papagno, L

AU - Appay, V

AU - Weekes, M

AU - Conlon, C

AU - Spina, C

AU - Little, S

AU - Screaton, G

AU - van der Merwe, A

AU - Richman, D D

AU - McMichael, A J

AU - Jones, E Y

AU - Rowland-Jones, S L

PY - 2004/12/20

Y1 - 2004/12/20

N2 - HIV-specific cytotoxic T lymphocytes (CTL) are important in controlling HIV replication, but the magnitude of the CTL response does not predict clinical outcome. In four donors with delayed disease progression we identified Vbeta13.2 T cell receptors (TCRs) with very similar and unusually long beta-chain complementarity determining region 3 (CDR3) regions in CTL specific for the immunodominant human histocompatibility leukocyte antigens (HLA)-B8-restricted human immunodeficiency virus-1 (HIV-1) nef epitope, FLKEKGGL (FL8). CTL expressing Vbeta13.2 TCRs tolerate naturally arising viral variants in the FL8 epitope that escape recognition by other CTL. In addition, they expand efficiently in vitro and are resistant to apoptosis, in contrast to FL8-specific CTL using other TCRs. Selection of Vbeta13.2 TCRs by some patients early in the FL8-specific CTL response may be linked with better clinical outcome.

AB - HIV-specific cytotoxic T lymphocytes (CTL) are important in controlling HIV replication, but the magnitude of the CTL response does not predict clinical outcome. In four donors with delayed disease progression we identified Vbeta13.2 T cell receptors (TCRs) with very similar and unusually long beta-chain complementarity determining region 3 (CDR3) regions in CTL specific for the immunodominant human histocompatibility leukocyte antigens (HLA)-B8-restricted human immunodeficiency virus-1 (HIV-1) nef epitope, FLKEKGGL (FL8). CTL expressing Vbeta13.2 TCRs tolerate naturally arising viral variants in the FL8 epitope that escape recognition by other CTL. In addition, they expand efficiently in vitro and are resistant to apoptosis, in contrast to FL8-specific CTL using other TCRs. Selection of Vbeta13.2 TCRs by some patients early in the FL8-specific CTL response may be linked with better clinical outcome.

U2 - 10.1084/jem.20032044

DO - 10.1084/jem.20032044

M3 - Article

VL - 200

SP - 1547

EP - 1557

JO - Journal of Experimental Medicine

JF - Journal of Experimental Medicine

IS - 12

ER -

HIV-specific cytotoxic T cells from long-term survivors select a unique T cell receptor

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