Abstract

TCRBV CDR3 repertoire diversity was analyzed in a cross-sectional study of HIV-infected individuals by CDR3 fingerprinting/spectratyping and single strand conformation polymorphism (SSCP). Most TCRBV families were detected in CD4+ cells of HIV-infected patients with CD4 counts ranging from 35 to 1103. In patients with CD4 counts >500, CD4+ TCRBV CDR3 fingerprinting profiles contained subtle variations with generally gaussian-distributed sizes. Lower CD4 counts coincided with more fragmented TCRBV CDR3 repertoires, containg dominant bands and bands missing from the CDR3 profiles. The CD8+ population of the same patients exhibited skewed CDR3 profiles of the majority of TCR BV families at CD4 counts >500. Irregularity of CD8+ CDR3 size distribution was most profound at low CD4 counts and suggested domination of the CD8+ TCRBV repertoire by a limited number of clones. Skewed patterns of CDR3 diversity probably reflect (oligo)clonal expansion of particular CD4+ and CD8+ cell populations during chronic infection with HIV. In addition, irregular CDR3 profiles of CD4+ and CD8+ at low CD4 counts suggest diminished TCR repertoire diversity, which may contribute to immunodeficiency.

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