ANALYSIS OF THE TCR V-GAMMA REPERTOIRE IN HEALTHY DONORS AND HIV-1-INFECTED INDIVIDUALS

During the course of infection with HIV-1, striking alterations in the subset distribution of peripheral blood gamma delta T cells are obser ved. While TCR V(delta)2 expression dominates among peripheral blood g amma delta T cells in healthy adults, there is a clear preponderance o f V(delta)1 cells in HIV-l-infected persons. In this study, we present the first flow cytometry (FCM) analysis of the complete TCR V-gamma g ene repertoire in HIV-l-infected individuals using a panel of mAb agai nst all expressed V-gamma genes. The quantitative analysis of TCR V-ga mma transcripts after amplification of cDNA by inverse PCR suggested t hat V(gamma)5 usage is increased in HIV-1(+) donors. This was confirme d by FCM with a new anti-V gamma 5 mAb. In addition, all members of th e TCR VgammaI gene family (i.e. V(gamma)2, 3, 4, 5 and 8) were express ed on significantly higher percentages of gamma delta T cells in HIVas compared to HIV- donors, whereas VgammaII (V(gamma)9) expression wa s drastically reduced. No preferential association of the expanded V(d elta)1(+) cells with a particular V-gamma gene was observed in HIV-1() donors. These results indicate that the increase in V(delta)1(+) cel ls during HIV-1 infection occurs independently of the V-gamma gene usa ge and support the hypothesis that a V(delta)1-selective ligand might be involved.