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

DC Douek, MR Betts, JM Brenchley, BJ Hill… - The Journal of …, 2002 - journals.aai.org
DC Douek, MR Betts, JM Brenchley, BJ Hill, DR Ambrozak, KL Ngai, NJ Karandikar…
The Journal of Immunology, 2002journals.aai.org
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 …
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.
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