NDLI: Molecular and Functional Analysis of a Conserved CTL Epitope in HIV-1 p24 Recognized from a Long-Term Nonprogressor: Constraints on Immune Escape Associated with Targeting a Sequence Essential for Viral Replication

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Molecular and Functional Analysis of a Conserved CTL Epitope in HIV-1 p24 Recognized from a Long-Term Nonprogressor: Constraints on Immune Escape Associated with Targeting a Sequence Essential for Viral Replication

Content Provider	Scilit
Author	Wagner, Ralf Leschonsky, Bernd Harrer, Ellen Paulus, Christina Weber, Christine Walker, Bruce D. Buchbinder, Susan Wolf, Hans Kalden, Joachim R. Harrer, Thomas
Copyright Year	1999
Description	It has been hypothesized that sequence variation within CTL epitopes leading to immune escape plays a role in the progression of HIV-1 infection. Only very limited data exist that address the influence of biologic characteristics of CTL epitopes on the emergence of immune escape variants and the efficiency of suppression of HIV-1 by CTL. In this report, we studied the effects of HIV-1 CTL epitope sequence variation on HIV-1 replication. The highly conserved HLA-B14-restricted CTL epitope DRFYKTLRAE in HIV-1 p24 was examined, which had been defined as the immunodominant CTL epitope in a long-term nonprogressing individual. We generated a set of viral mutants on an HX10 background differing by a single conservative or nonconservative amino acid substitution at each of the P1 to P9 amino acid residues of the epitope. All of the nonconservative amino acid substitutions abolished viral infectivity and only 5 of 10 conservative changes yielded replication-competent virus. Recognition of these epitope sequence variants by CTL was tested using synthetic peptides. All mutations that abrogated CTL recognition strongly impaired viral replication, and all replication-competent viral variants were recognized by CTL, although some variants with a lower efficiency. Our data indicate that this CTL epitope is located within a viral sequence essential for viral replication. Targeting CTL epitopes within functionally important regions of the HIV-1 genome could limit the chance of immune evasion.
Ending Page	3734
Page Count	8
Starting Page	3727
ISSN	00221767
e-ISSN	15506606
DOI	10.4049/jimmunol.162.6.3727
Journal	The Journal of Immunology
Issue Number	6
Volume Number	162
Language	English
Publisher	The American Association of Immunologists
Publisher Date	1999-03-15
Access Restriction	Open
Subject Keyword	Viral Replication Ctl Epitope Essential for Viral Sequence Essential
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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