Analysis of the T-cell receptor beta-chain variable-region (V beta) repertoire in monozygotic twins discordant for human immunodeficiency virus: evidence for perturbations of specific V beta segments in CD4+ T cells of the virus-positive twins.

Abstract

We analyzed the T-cell receptor (TCR) V beta repertoire in human immunodeficiency virus type 1 (HIV-1)-infected individuals at different stages of disease. To circumvent the effect of HLA and other loci on the expressed TCR repertoire, we compared the TCR repertoire in nine pairs of monozygotic twins who were discordant for HIV infection. A semiquantitative polymerase chain reaction (PCR) assay and flow cytometry enabled us to show distinct differences in the V beta repertoire in the HIV-positive twin compared with the HIV-negative twin. By combining PCR and cytofluorometry, these differences were restricted to a specific set of TCR V beta segments, with members of the V beta 13 family perturbed in six out of seven cases and those of the V beta 21 family perturbed in four out of seven cases studied. Most of the other V beta families remained unchanged. Our results provide direct evidence for a skewed TCR repertoire in HIV infection.