The T-cell repertoire is not dictated by self antigens alone

The influence of genetic and environmental factors on the functional cytotoxic T cell (CTL) allorepertoire was studied by comparing the CTL precursor frequencies against the same HLA alloantigens in 116 sibling pairs. A significantly different precursor frequency was found in 68%, 61% and 59% of siblings sharing 0, 1 and 2 HLA haplotypes, respectively. These data show that, although HLA is important in determining the T-cell repertoire, this is hardly reflected in the allorepertoire. Even 50% of the monozygotic twin pairs showed a significant disparity in their CTL allorepertoire, indicating that environmental factors play a role as well. The non-inherited maternal HLA antigens could be identified as one of the environmental factors shaping the CTL allorepertoire.