Differential patterns of T-cell receptor BV-specific activation of T cells by gp 120 from different HIV strains

Studies by several groups have suggested that HIV infection in vivo results in a BV-specific alteration of the TCR repertoire and that this might play a role in the pathogenesis of AIDS. Our earlier studies demonstrated that both a crude extract of HIV451 as well as purified gp160 from HIV451 could specifically activate, in vitro, T cells expressing a common set of TCRBV segments (TCRBV3, 12, 14, 15, and sometimes BV17 and 20) in individuals of disparate HLA type. Furthermore, purified gp120 from HIV451 was shown to have a similar ability to activate T cells, although with a slightly different TCRBV-specific pattern. In order to determine whether gp120 from other HIV strains could similarly activate T cells in a TCRBV-specific pattern, PBMC from HIV seronegative individuals of disparate HLA type were stimulated with gp120 from three strains of HIV (451, IIIB, and MN). The authors found that gp120 from all three strains activate T cells bearing TCRBV2 and BV3 in nearly every individual. T cells expressing other BV segments are also activated, but this is more variable and appears to be unique to each individual. Furthermore, gp120(451) and gp120 from HIVIIIB and HIVMN differ in their ability to activate T cells expressing these other TCRBV segments. These observations suggest that variation in the structure of gp120 and in the genetic and/or environmental background of the individual play an important role in determining which TCRBV segments are 'triggered' by gp120. Furthermore, these observations may have important implications for the rate of disease progression in HIV-infected individuals.