The T cell population is comprised of two distinct reciprocal subsets identifiable by UCHL1 and 2H4 antibodies. 2H4+ cells are virgin T cells and UCHL1+ cells are memory T cells. Previously it has been shown that dendritic cells (DC) form clusters with T cells. In this study we have examined the proportions of UCHL1+ and 2h4+ T cell subtypes in DC-T cell clusters. DC and T cells were purified from human peripheral blood and cultured in autologous or allogeneic combinations. Clusters, which were visible after culture for 24-48 h, were separated and the phenotype of the cells in the clusters was analyzed. It was found that the ratio of UCHL1+ and 2H4+ cells was the same among both clustered and nonclustered cells. Autologous clusters contained the same proportions of UCHL1+ and 2H4+ cells as allogeneic clusters. Experiments with separated UCHL1+ and UCHL1- T cells demonstrated that in autologous mixed leukocyte reaction mainly UCHL1- cells proliferated. Separated clusters were cultured for a total period of 7 days, which demonstrated that the majority of the T cells derived either from autologous or allogeneic clusters were UCHL1+ activated blasts. The remaining 2H4+ T cells resembled inactivated T cells. Thus it is concluded that the initial binding of T cells to autologous or allogeneic DC is mediated by a mechanism which is unaffected by the differentiation of virgin T cells into memory T cells. The low proliferative response of memory T cells to autologous DC suggested that clustering with DC does not necessarily lead to proliferative activity. Autoreactive T cells do not differ from alloreactive cells in acquiring the antigenic phenotype of memory T cells after activation.