HIV-specific cytotoxic T cells from long-term survivors select a unique T cell receptor.
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.
Dong
Tao
T
Medical Research Council Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford OX3 9DS UK.
Stewart-Jones
Guillaume
G
Chen
Nan
N
Easterbrook
Philippa
P
Xu
Xiaoning
X
Papagno
Laura
L
Appay
Victor
V
Weekes
Michael
M
Conlon
Chris
C
Spina
Celsa
C
Little
Susan
S
Screaton
Gavin
G
van der Merwe
Anton
A
Richman
Douglas D
DD
McMichael
Andrew J
AJ
Jones
E Yvonne
EY
Rowland-Jones
Sarah L
SL
D017209:Apoptosis / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D015693:Gene Products, nef / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology* / Q000473:pathology; D015497:HIV-1 / Q000276:immunology* / Q000502:physiology; D015795:HLA-B8 Antigen / Q000276:immunology*; D006801:Humans; D008297:Male; D009842:Oligopeptides / Q000276:immunology; D011379:Prognosis; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014779:Virus Replication / Q000276:immunology; D054311:nef Gene Products, Human Immunodeficiency Virus
D018984:Epitopes, T-Lymphocyte; D015693:Gene Products, nef; D015795:HLA-B8 Antigen; D009842:Oligopeptides; D016693:Receptors, Antigen, T-Cell, alpha-beta; D054311:nef Gene Products, Human Immunodeficiency Virus