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.


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).


CONCLUSIONS
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.
Killian
M Scott
MS
AIDS Institute and Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California 90095, USA.
Sabado
Rachel Lubong
RL
Kilpatrick
Stephanie
S
Hausner
Mary Ann
MA
Jamieson
Beth D
BD
Yang
Otto O
OO
D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D017637:Clonal Deletion; D002999:Clone Cells / Q000276:immunology; D022801:Complementarity Determining Regions / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005434:Flow Cytometry / Q000379:methods; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1; D006801:Humans; D007111:Immunity, Cellular; D008297:Male; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods
D022801:Complementarity Determining Regions; D018984:Epitopes, T-Lymphocyte; D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta