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Biomedical subjects

L Moretta

Publications and source records attributed to L Moretta.

312 records · Page 18Linked to original sources

Human interleukin-2 promotes proliferation of activated B cells via surface receptors similar to those of activated T cells.

Human interleukin-2 (IL-2) is a glycoprotein of relative molecular mass (Mr) 15,000, which is released by T lymphocytes on stimulation with antigen or mitogen and functions as a T-cell growth factor (TCGF) by inducing proliferation of activated T cells. It is generally accepted that resting or activated B cells do not respond directly to IL-2 but require for their proliferation other T-cell-derived lymphokines usually referred to as B-cell growth factors (BCGFs). Recently, however, a monoclonal antibody reacting with the IL-2 receptor molecules expressed by activated T cells (anti-Tac) was shown to react also with certain B tumour cells; in addition, murine B cells proliferate in response to pure human IL-2. We now show that recombinant IL-2, derived from Escherichia coli expressing the human gene, is able to promote strong proliferation of human B cells activated with protein-A-rich Staphylococcus aureus Cowans strain I. Moreover, we demonstrate that the anti-Tac antibody also reacts with S. aureus-activated normal B cells and inhibits sharply the proliferative response of such cells to IL-2. Finally, immunoprecipitation experiments reveal that anti-Tac defines similar molecules on activated T and B cells.

Animals↗

Human natural killer cell receptors: insights into their molecular function and structure.

NK cells express receptors characterized by opposite functions that finely regulate their activities. Among inhibitory receptors, some are specific for different groups of MHC class I alleles, while others are still orphan receptors. On the contrary, various activating receptors are involved in the triggering of NK-mediated natural cytotoxicity. In general, their engagement induces human NK cells to kill target cells that are either HLA class I-negative or -deficient. Thus, the process of NK cell triggering mediated by Natural Cytotoxicity Receptors can be mainly considered as a non MHC-restricted mechanism. Here, a brief description of the molecular nature of these receptors, as well as, of their 3D-structures and of the implications for ligand recognition, is given.

Antigens, CD↗

Phenotypic and functional characterization of human T lymphocytes expressing a gamma/delta T cell antigen receptor.

Most mature T lymphocytes express CD3-associated antigen receptor molecules (TCR) formed by alpha and beta chains. Recently, a minor subset has been identified that express a different CD3-associated TCR composed of gamma and delta chains. The cell subset expressing TCR gamma/delta differs from conventional T cells in a number of phenotypic and functional characteristics. The simultaneous lack of both CD4 and CD8 antigens at the cell surface allows one to greatly enrich for TCR gamma/delta + cells (by monoclonal antibodies, mAbs and complement). Cloning of CD4-8- peripheral blood lymphocytes revealed that they are homogeneously composed of cytolytic cells which, in most instances, lyse tumor target cells. TCR gamma/delta + cells proliferated in response to allogeneic cells in mixed lymphocyte culture (MLC) and MLC-derived TCR gamma/delta + cells specifically lysed PHA-induced blast cells bearing the stimulating alloantigens, thus providing the formal proof that they recognize (allo)antigens. The use of different mAbs specific for TCR gamma/delta molecules allowed us to identify two distinct subsets which bound BB3 and delta-TCS-1 mAbs, respectively. The BB3-reactive molecules in peripheral blood-derived TCR gamma/delta + cells were represented by C gamma 1-encoded disulphide-linked heterodimers, whereas delta-TCS-1 reacted with C gamma 2-encoded non disulphide-linked molecules. Both BB3 and delta-TCS-1 mAb induced activation of cloned cells expressing the corresponding antigenic determinants (as assessed by measurements of intracellular Ca++ and/or lymphokine production or cytolytic activity).(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗