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) gamma-gene and a second glycoprotein termed TCR delta (refs 1-4). TCR gamma delta is expressed on CD3+ thymocytes during fetal ontogeny before the appearance of TCR alpha-beta (alpha beta) (refs 5-7), on CD3+CD4-CD8- adult thymocytes, and on a subset (1-10%) of CD3+ cells in adult peripheral lymphoid organs and the peripheral blood. TCR gamma delta-expressing T cells probably represent a distinct mature T-cell lineage with the capacity to proliferate in response to receptor-mediated signals, and to display non-major histocompatibility complex (MHC)-restricted cytolysis. Critical to understanding the function of this T-cell subset is the identification of the ligand(s) recognized by TCR gamma delta. Here we describe an alloreactive CD3+CD4-CD8-TCR gamma delta-expressing, TCR alpha beta-negative, T-cell line that manifests MHC-linked recognition specificity for both proliferation and cytotoxicity. Our results suggest that T cells expressing TCR gamma delta are capable of self-non-self MHC discrimination and that they can undergo MHC-influenced selection during differentiation like TCR alpha beta-expressing T cells.

Site-restricted persistent cytomegalovirus infection after selective long-term depletion of CD4+ T lymphocytes.

“…It is now established that T lymphocytes of this subset express a TCR-y/S (35)(36)(37)(38) and are capable of performing nonrestricted (39,40) as well as MHC-linked specific cytolytic functions (41,42).…”

Predominant variable region gene usage by gamma/delta T cell receptor-bearing cells in the adult thymus.

“…It is useful to consider the relatively limited diversity of expressed Vy and V8 genes in the context of a recent report demonstrating alloreactive y/8 cells specific for an MHC-linked antigen (38). The target class I antigen was shown to be encoded by a gene in the H-2-D or linked Qa/Tla regions .…”

Diversity of γδ T-cell antigens

“…25,26 The pair of related T-locus Ags, Diverse cd T-cell antigens WK Born et al 14 T10/22, may be considered prototypic, because crystal structures of these Ags, as well as of a cd TCR engaged with T22, have been available for some time now. 27,28 These structures show that the T Ags do not present peptides, and that the cd TCR (KN6) binds to T22 at an angle, mainly using CDR3d amino-acid side chains for the interaction.…”