Numerous virus-specific, class I-restricted cytotoxic T lymphocyte (CTL) epitopes have been identified, yet little information is available regarding the specificity of the CTL response in persons of the same human histocompatibility leukocyte antigen (HLA) type. In this study, the human immunodeficiency virus (HIV) 1 envelope-specific CTL response was evaluated in five HLA-B14-positive persons. CTL responses specific for a previously described nine-amino acid epitope in gp41 (aa 584-592, ERYLKDQQL) could be identified in all subjects, and CTL clones specific for this epitope could be isolated from four persons. Despite heterogeneous T cell receptor usage, the fine specificity of the clones was similar, as defined by recognition of alanine-substituted peptides as well as peptides representing natural HIV-1 sequence variants. Correlation with in vivo virus sequences revealed that the dominant species in two of the subjects represented poorly recognized variants, with a K-->Q substitution at amino acid 588, whereas no variants were observed in the other two subjects. Although clonal type-specific responses to these dominant variants could be identified, the magnitude of these responses remained small, and the dominant CTL response was directed at the minor in vivo variant. These studies indicate that despite similar epitope-specific immunologic pressure in persons of the same HLA type, the in vivo quasispecies may differ, and that the major in vivo immune response to a given CTL epitope can be directed at a minor variant.
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April 01 1996
T cell receptor usage and fine specificity of human immunodeficiency virus 1-specific cytotoxic T lymphocyte clones: analysis of quasispecies recognition reveals a dominant response directed against a minor in vivo variant.
S A Kalams,
S A Kalams
AIDS Research Center and Infectious Disease Unit, Massachusetts General Hospital, Boston, 02114, USA.
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R P Johnson,
R P Johnson
AIDS Research Center and Infectious Disease Unit, Massachusetts General Hospital, Boston, 02114, USA.
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M J Dynan,
M J Dynan
AIDS Research Center and Infectious Disease Unit, Massachusetts General Hospital, Boston, 02114, USA.
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K E Hartman,
K E Hartman
AIDS Research Center and Infectious Disease Unit, Massachusetts General Hospital, Boston, 02114, USA.
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T Harrer,
T Harrer
AIDS Research Center and Infectious Disease Unit, Massachusetts General Hospital, Boston, 02114, USA.
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E Harrer,
E Harrer
AIDS Research Center and Infectious Disease Unit, Massachusetts General Hospital, Boston, 02114, USA.
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A K Trocha,
A K Trocha
AIDS Research Center and Infectious Disease Unit, Massachusetts General Hospital, Boston, 02114, USA.
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W A Blattner,
W A Blattner
AIDS Research Center and Infectious Disease Unit, Massachusetts General Hospital, Boston, 02114, USA.
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S P Buchbinder,
S P Buchbinder
AIDS Research Center and Infectious Disease Unit, Massachusetts General Hospital, Boston, 02114, USA.
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B D Walker
B D Walker
AIDS Research Center and Infectious Disease Unit, Massachusetts General Hospital, Boston, 02114, USA.
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S A Kalams
AIDS Research Center and Infectious Disease Unit, Massachusetts General Hospital, Boston, 02114, USA.
R P Johnson
AIDS Research Center and Infectious Disease Unit, Massachusetts General Hospital, Boston, 02114, USA.
M J Dynan
AIDS Research Center and Infectious Disease Unit, Massachusetts General Hospital, Boston, 02114, USA.
K E Hartman
AIDS Research Center and Infectious Disease Unit, Massachusetts General Hospital, Boston, 02114, USA.
T Harrer
AIDS Research Center and Infectious Disease Unit, Massachusetts General Hospital, Boston, 02114, USA.
E Harrer
AIDS Research Center and Infectious Disease Unit, Massachusetts General Hospital, Boston, 02114, USA.
A K Trocha
AIDS Research Center and Infectious Disease Unit, Massachusetts General Hospital, Boston, 02114, USA.
W A Blattner
AIDS Research Center and Infectious Disease Unit, Massachusetts General Hospital, Boston, 02114, USA.
S P Buchbinder
AIDS Research Center and Infectious Disease Unit, Massachusetts General Hospital, Boston, 02114, USA.
B D Walker
AIDS Research Center and Infectious Disease Unit, Massachusetts General Hospital, Boston, 02114, USA.
Online ISSN: 1540-9538
Print ISSN: 0022-1007
J Exp Med (1996) 183 (4): 1669–1679.
Citation
S A Kalams, R P Johnson, M J Dynan, K E Hartman, T Harrer, E Harrer, A K Trocha, W A Blattner, S P Buchbinder, B D Walker; T cell receptor usage and fine specificity of human immunodeficiency virus 1-specific cytotoxic T lymphocyte clones: analysis of quasispecies recognition reveals a dominant response directed against a minor in vivo variant.. J Exp Med 1 April 1996; 183 (4): 1669–1679. doi: https://doi.org/10.1084/jem.183.4.1669
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