Human T lymphocytes expressing [formula omitted] T cell antigen receptor

Abstract

The majority of mature T lymphocytes express CD3-associated antigen receptor molecules (TCR) formed by α and β chains. Recently, a minor subset has been identified that expresses a different CD3-associated heterodimer composed of γ and δ chains. The TCR γ δ + cell subset differs from conventional T cells for a number of phenotypic and functional characteristics. The simultaneous lack of both CD4 and CD8 antigens allows to greatly enrich TCR γ δ + cells (by monoclonal antibodies and complement). Cloning of CD4-8- peripheral blood lymphocytes, under limiting dilution conditions, revealed that they are homogeneously composed of cytolytic cells which, in most instances, lyse tumor target cells. The formal proof has been provided that TCR γ δ + cells are able to recognize antigens. Indeed they proliferated in response to allogeneic cells in mixed lymphocyte culture (MLC) and MLC-derived TCR γ δ + cells specifically lysed PHA-induced blast cells bearing the stimulating alloantigens. The use of different monoclonal antibodies specific for TCR γ δ molecules allowed to identify two distinct subsets which bound BB3 and δ-TCS-1 mAbs, respectively. The BB3-reactive TCR molecules were represented by Cγ1-encoded disulfide-linked heterodimers, whereas δ-TCS-1 reacted with Cγ2-encoded nondisulfide-linked molecules. Both BB3 and δ-TCS-1 mAb induced activation of cloned cells expressing the corresponding antigenic determinants (as assessed by measurements of intracellular Ca 2+ and lymphokine production or cytolytic activity). Analysis of the unfrequent δ-TCS-1 + clones which express surface CD8 molecules revealed that the “heavy” 55 kDa form of (Cγ2-encoded) γ chain is selectively expressed by this cell type. Analysis of the distribution of subsets expressing different TCR γ δ isotypes showed that the Cγ1-encoded, BB3-reactive form is prevalent in the peripheral blood, but virtually absent in the thymus. In contrast, cells expressing the Cγ2-encoded, δ-TCS-1 reactive form are relatively unfrequent in peripheral blood, but represent the majority of TCR γ δ + thymocytes . In addition, upon culture in rIL-2, approximately half of the δ-TCS-1 + thymocytes expressed CD8 antigen, thus providing further evidence that major differences exist in the distribution of TCR γ δ + subsets in thymus and in peripheral blood.