title: The gamma T-cell antigen receptor.
abstract: The gamma-TCR is encoded by genes composed of V, J, and C elements that demonstrate a limited potential for recombinational diversity. These genes are rearranged, transcribed, and translated into proteins early during thymic ontogeny. Lymphocytes express gamma-TCR proteins on the plasma membrane only in association with the CD3 complex. gamma-TCR glycoproteins usually associate with another non-gamma glycoprotein, designated delta-TCR, to form a heterodimer receptor. Both non-disulfide-bonded and disulfide-bonded gamma/delta-TCR heterodimers have been identified on the plasma membrane of human T lymphocytes. On certain gamma-TCR-bearing T cell lines, a delta-TCR protein cannot be visualized by autoradiography. It is possible that delta-TCR proteins are associated with gamma-TCR glycoproteins on these cell lines but are not efficiently radiolabeled. Alternatively, it has been suggested that homodimers of gamma-TCR proteins can assemble with CD3 and be expressed on the plasma membrane of these cells. In adult lymphoid tissues, the majority of T lymphocytes expresses a CD3, alpha/beta antigen receptor, whereas only a minor subset (less than 5% of peripheral blood lymphocytes, lymph node, spleen, and thymocytes) express a CD3, gamma/delta antigen receptor. IL-2-dependent cell lines of both murine and human CD3, gamma/delta T cells have been established. Most CD3, gamma/delta T cell lines mediate cytotoxicity against a broad spectrum of tumor-cell targets, although the functional significance of this observation remains unclear. Cytotoxicity is apparently not restricted by or directed against MHC antigens. Antibodies against CD3 or gamma-TCR can induce proliferation and IL-2 secretion and can either augment or inhibit cytotoxicity, demonstrating that the gamma/delta-TCR is a functional receptor. The ligand recognized by this receptor has not been identified. The physiological role of T lymphocytes expressing gamma/delta-TCR, the molecular and structural properties of delta-TCR, and the relationship between CD3, alpha/beta T lymphocytes and CD3, gamma/delta T lymphocytes are the major unresolved questions that will be the primary focus of further experimentation.
authors.affiliation: Becton Dickinson Monoclonal Center, Inc., Mountain View, California 94043.
authors.forename: L L
authors.initials: LL
authors.lastname: Lanier
authors.forename: A T
authors.initials: AT
authors.lastname: Serafini
authors.forename: J J
authors.initials: JJ
authors.lastname: Ruitenberg
authors.forename: S
authors.initials: S
authors.lastname: Cwirla
authors.forename: N A
authors.initials: NA
authors.lastname: Federspiel
authors.forename: J H
authors.initials: JH
authors.lastname: Phillips
authors.forename: J P
authors.initials: JP
authors.lastname: Allison
authors.forename: A
authors.initials: A
authors.lastname: Weiss
mesh_terms: D000937:Antigen-Antibody Reactions; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D006801:Humans; D011971:Receptors, Immunologic / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D000945:Antigens, Differentiation, T-Lymphocyte; D011971:Receptors, Immunologic