Clonal breadth of the HIV-1-specific T-cell receptor repertoire in vivo as determined by subtractive analysis

Objective: Although the epitopic breadth of HIV-1 -specific CD8 T lymphocyte (CTL) responses has been described, the T cell receptor (TCR) diversity of virus-specific cells remains poorly defined. Design and methods: To address this issue, we applied a novel technique for subtractive analysis of the HIV-1-specific CTL repertoire, combining specific deletion of peptide-specific cells by 5-fluorouracil with TCR spectratyping to identify clonal breadth of CTL recognizing individual peptides. Results: Comprehensive analysis of an infected individual reveals that nine identified HIV-1 -specific responses are comprised of at least 38 distinct T-cell clones (ranging from two to 10 distinct clones per epitope). Conclusion: Given the potentially crucial role of T-cell receptor breadth for viral recognition and avoidance of escape, this subepitopic analysis of CTL may offer an important measure of cellular immunity for pathogenesis and vaccine studies. (c) 2005 Lippincott Williams & Wilkins.