THE INFLUENCE OF NON-HLA GENES ON THE HUMAN T-CELL RECEPTOR REPERTOIRE

We previously demonstrated a central role for HLA genes in determining the T-cell receptor (TCR) repertoire. However, these studies also sug gested that other genetic factors might also play a role in the develo pment of this repertoire. In order to assess the role of non-HLA genes in the development of the TCR repertoire, we have analysed and compar ed the TCR repertoires of individuals in three families consisting of both monozygotic twins as well as an HLA-identical sib. TCR repertoire analysis was performed with both V-segment-specific MoAb and the poly merase chain reaction using TCRBV-segment-specific oligonucleotide pri mers. We observed that in every case the TCR repertoires of identical twins were more similar to each other than to their HLA-identical sib. Furthermore, in one family we were able to show by genotype analysis that most of the differences in repertoire between the identical twins and their HLA-identical sib were caused by polymorphisms in the TCR g enes that influence expression levels. These studies document an impor tant role for non-HLA genes in determining the TCR repertoire in man a nd raise the possibility that such TCR polymorphisms may play a signif icant role in determining disease susceptibility.