A physiological ligand of positive selection is recognized as a weak agonist.

Positive selection is a process that ensures that peripheral T cells express TCR that are self-MHC restricted. This process occurs in the thymus and requires both self-MHC and self-peptides. We have recently established a TCR transgenic (TCR(trans)(+)) mouse model using the C10.

A physiological ligand of positive selection is seen with high specificity.

Positive selection is a process that ensures that peripheral T cells express TCR that are restricted to self-MHC molecules. This process requires both self-MHC and self-peptides. We have recently established a TCR transgenic mouse model (C10.

Liposome encapsulated aurothiomalate reduces collagen-induced arthritis in DBA/1J mice.

Collagen-induced arthritis (CIA) generated in rats or mice has long been a model system for the study of rheumatoid arthritis in humans. In particular, this system has been used to study the mechanisms and effects of anti-arthritic drugs in the treatment of the disease. Sodium aurothiomalate (ATM) is an agent often used to treat rheumatoid arthritis in humans; however, it possesses inherent toxicities which limits its usefulness.

Treatment of an autoimmune disease with "classical" T cell veto: a proposal.

Immune responses protect against infectious diseases and cancers. In normal circumstances, the immune system is tolerant to self. However, under certain conditions this tolerance is broken.

Positive selection of an H2-M3 restricted T cell receptor.

Thymocytes are positively selected for alphabeta T cell antigen receptors (TCR) that recognize antigen in conjunction with self-major histocompatibility complex (MHC) molecules. MHC bound peptides participate in positive selection; however, their role has remained controversial. A TCR transgenic mouse was established using a TCR restricted to the MHC class Ib molecule, H2-M3.

H2-M3 restricted presentation of a Listeria-derived leader peptide.

Protective immunity to infection by many intracellular pathogens requires recognition by cytotoxic T lymphocytes (CTLs) of antigens presented on major histocompatibility complex (MHC) class I molecules. To be presented for recognition by pathogen-specific CTLs, these antigens must gain access to the host cell class I processing pathway. In the case of intracellular bacterial pathogens, the majority of bacterial proteins are retained within the bacterial membrane and therefore remain inaccessible to the host cell for antigen processing.

Specific inhibition of CD4+ T lymphocytes by a hybrid antibody.

T lymphocytes are crucial in the defense against foreign intruders and cancerous growths. Yet, in circumstances such as transplantation or autoimmunity, T-cell-mediated responses can be detrimental. Inhibition of these deleterious responses is currently achieved by drugs that induce general immune suppression.

Hybrid antibody mediated veto of cytotoxic T lymphocyte responses.

Strategies are being sought that allow the induction of specific tolerance to allogeneic transplants without affecting other immune functions. The so-called veto effect has been described as one such technology where CD8+ cells suppress responses of class I MHC-restricted T-lymphocyte precursors to antigens expressed by those CD8+ veto cells. Yet, veto inhibition will not be able to provide complete tolerance to allogeneic grafts since it only operates on cell populations that express CD8.

Permissive recognition during positive selection.

In the periphery alpha beta T lymphocytes recognize antigens in conjunction with major histocompatibility complex (MHC) molecules. In the thymus immature T cells are positively selected on MHC molecules in the apparent absence of cognate peptides. Thus, at different developmental stages a T cell responds to different epitopes, yet uses the identical alpha beta T cell antigen receptor (TcR).

Expression of Fc gamma RIII defines distinct subpopulations of fetal liver B cell and myeloid precursors.

We have isolated four distinct fetal liver (FL) populations based on the expression of AA4.1 and the low-affinity Fc gamma receptors type II and III (Fc gamma RII/III), and characterized them with respect to B cell, T cell, and myeloid precursor content. Polymerase chain reaction analysis revealed that the prevalent Fc gamma R isoform at this stage of FL development (day 12 of gestation) was Fc gamma RIII.

T cell receptor V beta 8.2 gene germ-line transcription: an early event of lymphocyte differentiation.

Rearrangement of the T cell antigen receptor (TCR) beta chain genes is highly regulated in both a developmental and a tissue-specific manner. T cell precursors originate from the yolk sac or fetal liver during gestation and from the bone marrow during adulthood. They initiate the recombination of TCR genes primarily during differentiation in the thymus.

How are alpha beta T cells positively selected in the thymus?

Thymus-derived (T) lymphocytes have the potential to express antigen receptors (TCR) that can recognize both self, as well as foreign antigens as they appear on the cell surface. In the thymus, positive selective allows the maturation of T cells that are able to see foreign antigens in conjunction with molecules encoded by genes of the major histocompatibility complex (MHC), whereas negative selection deletes auto-aggressive T cells. Control of T cell development is the only known function of the thymus.

Thymic education--T cells do it for themselves.

The phenomenon of positive selection of developing T cells is well established. However, the cellular interactions that are responsible for selecting the restriction element are still ill defined. Here, Tomasz Pawlowski and Uwe Staerz discuss the latest developments in the field, as well as some new evidence suggesting that cells of epithelial or hematopoietic origin are not the only ones capable of selecting the restriction element for T cells expressing the alpha beta T-cell receptor.

Positive selection of T lymphocytes on fibroblasts.

Thymocytes are selected for expression of alpha beta T-cell antigen receptors (TCR) which recognize antigen in conjunction with self-major histocompatibility complex (MHC) molecules. In the thymus the restriction element is imprinted on radioresistant stromal elements and on cells of haematopoietic origin. In mice negative for beta 2-microglobulin that are devoid of mature cytotoxic T lymphocytes, we find that intrathymic injection of different fibroblasts causes the maturation of CD4-CD8+TCRhigh thymocytes with distinct patterns of TCR V beta distribution.

[Monoclonal hybrid antibodies. New perspectives for basic research and tumor therapy].

Monoclonal hybrid antibodies are bi-specific constructs of two monoclonal antibodies with defined specificity. Hybrid antibodies can be used to force interactions between cell populations that under normal circumstances would not react with one another. Applications include the field of basic research as well as employment in therapy of malignancies and infectious diseases.

Establishment and characterization of lymphoid and myeloid mixed-cell populations from mouse late embryoid bodies, "embryonic-stem-cell fetuses".

Mouse embryonic stem (ES) cells have the potential to differentiate into embryoid bodies in vitro and mimic normal embryonic development. The "ES fetus" is a specific development at a late stage seen under our culture conditions. We have established several mixed populations from ES fetuses by using combinations of retroviruses carrying different oncogenes (v-abl, v-raf, c-myc), interleukins 2 and 3, and Con A.

Macrophages as accessory cells for class I MHC-restricted immune responses.

Ag do not elicit T lymphocyte responses unless they are presented in conjunction with MHC molecules on the surface of an appropriate APC. In the case of CD4+ T lymphocytes dendritic cells can deliver all signals required for complete induction as can macrophages and (activated) B cells. The function of CTL also depends on the presence of specialized accessory cells.

Recruitment of alloreactive cytotoxic T lymphocytes by an antigenic peptide.

To investigate the requirements for induction of cytotoxic T lymphocytes (CTL) by peptides we chose the 16-residue nucleoprotein peptide (NPP; 365-380) from the influenza virus A/NT/60/68 as model substrate that is recognized in conjunction with major histocompatibility complex H-2d. Here we present that CTL can be raised from naive animals by repeated in vitro stimulation with high concentrations of peptide. The frequency of this response can be boosted by immunization of the animals with NPP-conjugated to ovalbumin as a carrier.

Redirecting the cellular immune response.

A technology is described which combines the power of T lymphocytes in eliminating unwanted cells and causing beneficial inflammatory reactions with the great advantages of monoclonal antibodies. We show that heteroconjugate antibodies and hybrid antibodies, in which one of the component binding sites is anti-T-cell receptor and the other component binding is directed against any chosen target antigen, can focus T cells to act at the targeted site. We present experimental evidence for the in vitro efficacy of this system in viral infections and in the elimination of tumor cells.

Thymic selection process induced by hybrid antibodies.

Thymus-derived (T) lymphocytes using the alpha beta T-cell antigen receptor (TCR) recognize fragmented antigen in conjunction with surface molecules encoded by genes of the major histocompatibility complex (MHC). Peripheral T lymphocytes preferentially see antigen presented by self rather than by foreign MHC molecules, and autoreactive T lymphocytes are deleted. Thus, the peripheral T-lymphocyte repertoire is skewed towards recognition of antigen in the context of self-MHC and towards tolerance to self-antigens.

Tolerance in T-cell-receptor transgenic mice involves deletion of nonmature CD4+8+ thymocytes.

The mechanism of self-tolerance is studied in T-cell-receptor transgenic mice expressing a receptor in many of their T cells for the male (H-Y) antigen in the context of class I H-2Db MHC antigens. Autospecific T cells are deleted in male mice. The deletion affects only transgene-expressing cells with a relatively high surface-density of CD8 molecules, including nonmature CD4+ CD8+ thymocytes, and is not caused by anti-idiotype cells.

Self-tolerance eliminates T cells specific for Mls-modified products of the major histocompatibility complex.

In mice the product of the Mlsa locus is an unusual antigen capable of interaction with certain products of the major histocompatibility locus (MHC) to form a ligand for a large portion of the T-cell alpha/beta receptor repertoire, including nearly all receptors that use V beta 8.1. The presence of Mlsa/MHC during T-cell development results in the deletion of T cells that express V beta 8.