Biased TCR repertoire in HIV-1-infected patients due to clonal expansion of HIV-1-reverse transcriptase-specific CTL clones.
To study whether an expansion of HIV-1-specific CTL is contributing to the skewed TCR repertoire in HIV-1-infection, we characterized the TCR usage of CTL clones specific for a conserved epitope in HIV-1 reverse transcriptase (RT/476-484). CTL clones from three HIV-1-infected patients displayed highly similar TCR usage and used the identical Vbeta6.1 and Valpha2.5 gene segments. CTL clones from two patients showed a very high degree of similarity within the TCR complementarity-determining region-3 (CDR-3). In accordance with the similar molecular structure, all three CTL clones also exhibited a similar functional activity with regard to recognition of variant peptides and cytokine secretion pattern. In one subject clonal expansion of a single CTL specificity could be shown over a 10-mo period. TCR spectratyping of PBMC from two patients revealed a marked expansion of CDR-3 segments of a certain length within the Vbeta6-family. Sequence analysis of these CDR-3 yielded sequences identical to the RT/476-484-specific CTL previously isolated from the same patients. This analysis demonstrates that clonal expansion of HIV-1-specific CTL is contributing to the skewed TCR repertoire in HIV-1-infected patients.
Kolowos
W
W
Department of Medicine III, Institute of Clinical Immunology, University of Erlangen-Nuremberg, Germany.
Schmitt
M
M
Herrman
M
M
Harrer
E
E
Löw
P
P
Kalden
J R
JR
Harrer
T
T
D000595:Amino Acid Sequence; D001483:Base Sequence; D002469:Cell Separation; D002999:Clone Cells; D016207:Cytokines / Q000096:biosynthesis; D003602:Cytotoxicity, Immunologic; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D015332:Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D014644:Genetic Variation / Q000235:genetics / Q000276:immunology; D015658:HIV Infections / Q000276:immunology* / Q000378:metabolism; D054303:HIV Reverse Transcriptase / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis* / Q000235:genetics; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism*; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism
D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D009842:Oligopeptides; D016693:Receptors, Antigen, T-Cell, alpha-beta; D014764:Viral Proteins; D054303:HIV Reverse Transcriptase