A novel approach to the analysis of specificity, clonality, and frequency of HIV-specific T cell responses reveals a potential mechanism for control of viral escape

Daniel C Douek; Michael R Betts; Jason M Brenchley; Brenna J Hill; David R Ambrozak; Ka-Leung Ngai; Nitin J Karandikar; Joseph P Casazza; Richard A Koup

doi:10.4049/jimmunol.168.6.3099

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A novel approach to the analysis of specificity, clonality, and frequency of HIV-specific T cell responses reveals a potential mechanism for control of viral escape

Journal article

Peer reviewed

A novel approach to the analysis of specificity, clonality, and frequency of HIV-specific T cell responses reveals a potential mechanism for control of viral escape

Daniel C Douek, Michael R Betts, Jason M Brenchley, Brenna J Hill, David R Ambrozak, Ka-Leung Ngai, Nitin J Karandikar, Joseph P Casazza and Richard A Koup

The Journal of immunology (1950), Vol.168(6), pp.3099-3104

03/15/2002

DOI: 10.4049/jimmunol.168.6.3099

PMID: 11884484

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Abstract

Escape from the CD8(+) T cell response through epitope mutations can lead to loss of immune control of HIV replication. Theoretically, escape from CD8(+) T cell recognition is less likely when multiple TCRs target individual MHC/peptide complexes, thereby increasing the chance that amino acid changes in the epitope could be tolerated. We studied the CD8(+) T cell response to six immunodominant epitopes in five HIV-infected subjects using a novel approach combining peptide stimulation, cell surface cytokine capture, flow cytometric sorting, anchored RT-PCR, and real-time quantitative clonotypic TCR tracking. We found marked variability in the number of clonotypes targeting individual epitopes. One subject recognized a single epitope with six clonotypes, most of which were able to recognize and lyse cells expressing a major epitope variant that arose. Additionally, multiple clonotypes remained expanded during the course of infection, irrespective of epitope variant frequency. Thus, CD8(+) T cells comprising multiple TCR clonotypes may expand in vivo in response to individual epitopes, and may increase the ability of the response to recognize virus escape mutants.

CD8-Positive T-Lymphocytes - chemistry

Immunodominant Epitopes - immunology

Amino Acid Sequence

Immunodominant Epitopes - analysis

Epitopes, T-Lymphocyte - analysis

HIV - physiology

Humans

Middle Aged

Molecular Sequence Data

Epitopes, T-Lymphocyte - genetics

Virus Replication - immunology

HIV - immunology

Reverse Transcriptase Polymerase Chain Reaction

CD8-Positive T-Lymphocytes - virology

Receptors, Antigen, T-Cell, alpha-beta

Lymphocyte Count

Adult

Aged

Clone Cells

Epitopes, T-Lymphocyte - immunology

CD8-Positive T-Lymphocytes - immunology

Longitudinal Studies

Details

Title: Subtitle: A novel approach to the analysis of specificity, clonality, and frequency of HIV-specific T cell responses reveals a potential mechanism for control of viral escape
Creators: Daniel C Douek - Department of Experimental Transplantation and Immunology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. ddouek@mail.nih.gov
Michael R Betts
Jason M Brenchley
Brenna J Hill
David R Ambrozak
Ka-Leung Ngai
Nitin J Karandikar
Joseph P Casazza
Richard A Koup
Resource Type: Journal article
Publication Details: The Journal of immunology (1950), Vol.168(6), pp.3099-3104
DOI: 10.4049/jimmunol.168.6.3099
PMID: 11884484
NLM abbreviation: J Immunol
ISSN: 0022-1767
eISSN: 1550-6606
Publisher: United States
Language: English
Date published: 03/15/2002
Academic Unit: Pathology
Record Identifier: 9984046915302771

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