Pre-T-cell receptor

LEFl lymphoid enhancer-binding factor lisa 48-kDa nuclear protein expressed in pre-B and T cells. LEFl binds to a functionally important site in the T-cell receptor-alpha enhancer and confers maximal enhancer activity. LEFl belongs to a family of regulatory proteins that share homology with high mobility group protein-1. 

Harnett MM, Deehan MR, Williams DM et al. Induction of signalling anergy via the T-cell receptor in cultured Jurkat T-cells by pre-exposure to a filarial nematode secreted product. Parasite Immunology 1998 20(ll) 551-563. 

Perhaps the most astonishing aspect of this mAh is that it was used for the treatment of acute renal allograft rejection in patients only two years after being raised, on the basis of its ability to block CTLs in vitro, at a time when the structure of the T cell receptor complex was unknown (7). Although, even now it remains as an effective treatment for the reversal of steroid resistant acute allograft rejection, many of the compUcations associated with therapy were either underestimated or not anticipated. Nowadays extensive pre-clinical data is required, often involving primate studies, before a mAb can be used in clinical trials. It is likely that if mAbs to CDS were introduced today rather than in 1981 that they would not have gained a hcence for human use. Monoclonal antibodies to CDS in both human and animal studies have broadly similar effects and are of interest because they elicit many of the complications associated with mAb therapy. How these problems have been circumvented serves a framework for many other mAbs under development. 

Nagasawa T, Nakajima T, Tachibana K, et al. Molecular cloning and characterization of a murine pre-B-cell growth-stimulating factor/stromal cell-derived factor 1 receptor, a murine homolog of the human immunodeficiency virus 1 entry coreceptor fusin. Proc Natl Acad Sci U S A 1996 93 14726-14729. 

Rivino L, Messi M, Jarrossay D, Lanzavecchia A, Sallusto F, Geginat J. Chemokine receptor expression identifies Pre-T helper (Th)l, Pre-Th2, and nonpolarized cells among human CD4+ central memory T cells. J Exp Med 2004 200 725-735. 

Alacom B, Swamy M, Van-Santen HM, Schamel WW. 2006. T cell antigen receptor stoichiometry Pre-clustering for sensitivity. EMBO-Rep. 7 490-495. 

The cytokine IL-2 plays a key role in growth, differentiation, and activation of T-cells. The antibodies daclizumab and basiliximab, which recognize the a5 subunit of the IL-2 receptor (IL-2Ra) and block binding of IL-2, have been clinically effective as immunosuppressive agents [122], However for reasons of cost, administration, and possible side effects, they are used only pre- and post-transplantation, and in the acute phase of transplant rejection. This state of affairs has precipitated interest in small-molecule inhibition of this interaction. 

Activation of APCs (e.g., via toU-hke receptor, TLR) for the induction of costimulatory molecules, which is a pre-requisite for the induction of potent T cell responses [8]. 

Interleukin-7 (lL-7) plays an important role in stimulating the growth and differentiation of pre-B cells in the bone marrow (H15, S56). The major source of IL-7 in the bone marrow appears to be stromal cells (HIO, K14), upon which B-cell development in the bone marrow appears to be dependent (S56). IL-7 may also play a role in stimulating development of thymocytes (E14,03, S2) and also appears to stimulate proliferation and differentiation of mature T lymphocytes (B33, C18). Receptors for human IL-7 have been identified, cloned, and assigned to the hemopoietic growth factor receptor family (G17). 

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