ALLOSPECIFIC HELPER T-LYMPHOCYTE REPERTOIRE IN MONOZYGOTIC TWINS

In the course of maturation in the thymus there is a selection of T ly mphocytes based on the avidity between their T-cell receptors and HLA/ peptide complexes expressed on stromal thymic cells. The repertoire of mature T lymphocytes is further modulated by encounters with foreign antigens. Thus, the antigen specific repertoire of the peripheral T-ly mphocyte pool is determined by genetic and environmental factors. We r ecently reported that pairs of monozygotic twins often display signifi cant differences in their allospecific cytotoxic T-cell repertoire, su ggesting an important role of confrontation with foreign antigens on t he CD8(+) T-cell repertoire. We have now performed similar studies on the repertoire of allospecific CD4(+) T lymphocytes. Using positively selected CD4(+) T cells in limiting dilution analyses we compared the differences in the allospecific helper T-lymphocyte precursor frequenc ies (HTLpf) between pairs of genetically identical monozygotic twins a nd pairs of unrelated, HLA disparate individuals. We found that all mo nozygotic twin pairs and most unrelated pairs had similar HTLpf to the same stimulator, i.e. the 95% confidence intervals were overlapping. However, when studied in greater detail, the differences in HTLpf with in monozygotic twin pairs were found to be significantly smaller than the differences within pairs of unrelated responders. Thus, we find ev idence of an influence by environmental antigens also on the repertoir e of allospecific CD4(+) T cells, but polymorphic genetic factors seem to be more important here than for the repertoire of allospecific CD8 (+) T cells.