A unique T-cell receptor complex expressed on human fetal lymphocytes displaying natural-killer-like activity

Abstract

We have recently derived a series of cloned cell lines displaying natural killer (NK) cell-like activity from normal human fetal blood (25 weeks). The lines were obtained after repeated stimulation of mononuclear cells with allogeneic Epstein-Barr virus (EBV)-transformed B lymphocytes and are interleukin-2 (IL-2) dependent. Initial characterization of the clones has been reported previously. Certain of these clones have been found to have unusual surface characteristics, namely, they are recognized by several well-defined anti-T3 antibodies, but do not react with WT31, which is thought to recognise an invariant epitope of the human (Ti-alpha beta) structure. Transcription of the genes encoding the alpha- and beta-chains of the T-cell receptor was assessed in two of these clones (F6A4 and F6C7). Ti-beta genes were found to be expressed, whereas alpha messenger RNA was not detected in Northern blot analysis. These data strongly suggest that these cells do not produce a stoichiometric T3/Ti-alpha beta receptor complex. However, experiments performed with a monoclonal antibody (anti-NKFi) developed against F6C7 cells demonstrated the existence of a unique clonotypic structure [relative molecular mass (Mr) 85,000 (85K)] which is surface-associated with T3 proteins. Furthermore, both anti-T3 and anti-NKFi were found to block cytotoxic effector function. Together, the results support the view that T3 proteins are involved in non-major histocompatibility complex (MHC)-restricted cytotoxic reactions mediated by certain circulating fetal lymphocytes which are likely to use a clonotypic structure distinct from both the 'first' (alpha beta) and the putative 'second' (gamma delta) T-cell receptor to recognize their target. The present studies were designed to characterize this structure.

Adoptively transferred Vγ9Vδ2 T cells show potent antitumor effects in a preclinical B cell lymphomagenesis model

“…γδ T cells are attractive candidates for adoptive immunotherapy in human cancer patients because they mediate potent antitumor effects in an MHC-independent manner (1)(2)(3)(4), and therefore they do not require HLA matching of donors and recipients. Physiologically, γδ T cells are thought to be important for immunosurveillance (i.e., eradication of nascently transformed cells), since they can recognize early danger signals associated with neoplastic changes (5,6).…”

Disulfide-linked gamma delta T cell antigen receptors expressed on T cells derived from patients with primary immunodeficiency disorders.

“…Although only one 5-chain constant region gene segment has been identified (2-4), three different forms of the -chain have been demonstrated (1,(5)(6)(7)(8)(9)(10)(11)(12). These are: (a) A disulfide-linked '-chain polypeptide of 40 kD, coded by the Cy 1 gene segment, which is expressed on T cells derived from the peripheral blood or thymocytes from normal donors (1,9,10).…”

A novel subset of human lymphocytes with a T cell receptor-gamma complex.

“…One of these clones, termed F6C7, was used for mice immunizations. An mAb, designated anti-NKFi was found to identify on F6C7 lymphocytes a CD3-associated y chain (2,3) expressed either as a homodimer or possibly as part of an heterodimer (note that a S chain has remained undetected on F6C7 cells) . Anti-NKFi was shown to have a highly restricted clonotypic reactivity and could not therefore be used for characterization of lymphocyte subpopulations with a TCR-y complex.…”