Major histocompatibility complex-linked specificity of γδ receptor-bearing T lymphocytes

Abstract

Several recent studies have identified a distinct subset of CD3(T3)⁺CD4^–CD8^– T lymphocytes that express a CD3-associated heterodimer made up of the protein encoded by the T-cell receptor (TCR) γ-gene and a second glycoprotein termed TCRδ (refs 1-–4). TCRγδ is expressed on CD3⁺ thymocytes during fetal ontogeny before the appearance of TCR alpha-beta (αβ) (refs 5–7), on CD3⁺ CD4^–CD8^– adult thymocytes^4,6, and on a subset (1–10%) of CD3⁺ cells in adult peripheral lymphoid organs and the peripheral blood^1,8,9. TCRγδ-expressing T cells probably represent a distinct mature T-cell lineage with the capacity to proliferate in response to receptor-mediated signals^2,6, and to display non-major histocompatibility complex (MHC)-restricted cytoly-sis^2,10–13. Critical to understanding the function of this T-cell subset is the identification of the ligand(s) recognized by TCRγδ. Here we describe an alloreactive CD3⁺CD4^–CD8^–TCRγδ-expressing, TCRαβ-negative, T-cell line that manifests MHC-linked recognition specificity for both proliferation and cytotoxic-ity. Our results suggest that T cells expressing TCRγδ are capable of self-non-self MHC discrimination and that they can undergo MHC-influenced selection during differentiation like TCRαβ-expressing T cells.