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M T Scherer

Publications and source records attributed to M T Scherer.

9 recordsLinked to original sources
PubMed1996

B cells are not essential for peripheral T-cell tolerance.

Some self-reactive T cells avoid thymic tolerance and become mature peripheral cells. Nevertheless, these cells do not usually attack their hosts because T cells can be inactivated or killed, even after they are mature, by various means. The details of these processes are not fully understood; however, a number of experiments have suggested that peripheral tolerance may be induced in mature mouse T cells by exposure to antigen on resting B cells, cells that can express antigen bound to major histocompatibility complex proteins but that lack critical costimulatory molecules such as B7-1 and B7-2. Conversely, previous experiments have indicated that mature T cells can be stimulated by exposure to antigen on cells such as dendritic cells, cells that are thought to express the essential costimulatory molecules. We tested this idea in vivo by using mice that lack B cells. Unexpectedly, T-cell tolerance and antigen-induced T-cell death occurred normally in mice free of B cells. On the other hand, antigen-specific T-cell expansion in the spleens of such mice was impaired. Finally, we have recently shown that T-cell death in mice can be prevented by exposure to antigen and an inflammatory agent such as bacterial lipopolysaccharide. This was also true in mice that lacked B cells. Overall, these data show that mature T cells can be tolerized and rescued from tolerance in the absence of B cells.

Animals↗
PubMed1996

Endogenous Mtv-encoded superantigens are not required for development of murine AIDS.

Immune activation in murine AIDS (MAIDS) has been suggested to involve a superantigen (SAG). The possibility that SAGs encoded by mammary tumor virus (MTV) might be the source of stimulation was studied by using Mtv mice. Mtv- mice developed typical MAIDS, excluding a requirement for Mtv-encoded SAGs in the pathogenesis of this disorder.

Animals↗
PubMed1995

The use of mammary tumor virus (Mtv)-negative and single-Mtv mice to evaluate the effects of endogenous viral superantigens on the T cell repertoire.

Most laboratory strains of mice have between two and eight endogenous superantigens. These viral superantigens (vSAGs) are coded by genes in the 3' long terminal repeats of endogenous mammary tumor viruses (Mtv's). A line of Mtv-negative mice and several lines of mice containing single Mtv's were created by inbreeding the F2 progeny of CBA/CaJ and C58/J mice, which have no Mtv integrants in common. This allowed the T cell repertoire of H-2k mice, unaffected by Mtv superantigens, as well as the effects of vSAGs upon that repertoire, to be studied. Although each individual mouse had a different mix of C58/J and CBA/CaJ background genes, the T cell repertoires of different Mtv-negative mice were very similar and were reproducible. Since the background genes did not affect the V beta repertoire, there are no super-antigens, other than those encoded by Mtv's, that differ between CBA/CaJ and C58/J. CD4 and CD8 T cells had quite different repertoires in the Mtv-negative mice because of the effects of class I and class II major histocompatibility complex molecules on positive and negative selection. vSAG3 was found to delete V beta 5 T cells, while vSAG8 deleted V beta 7 T cells, and vSAG9 deleted V beta 13 T cells in addition to their previously reported specificities. vSAG17 deletes a small proportion of CD4+ T cells bearing V beta 11 and -12. vSAG14 and -30 have little effect on the T cell repertoire and are not expressed in thymocytes and splenocytes. An endogenous superantigen that has a low avidity for a particular V beta may positively select thymocytes, leading to an increased frequency of peripheral T cells bearing the relevant V beta s. We found evidence that vSAG11 may positively select T cells bearing V beta 8.2. Our data, which analyzed the effects of seven endogenous Mtv's, showed little evidence of positive selection by any other vSAGs on T cells bearing any V beta tested, despite published reports to the contrary.

Amino Acid Sequence↗
PubMed1994

Identification of two V beta 7-specific viral superantigens.

The commonly used strains of laboratory mice have mouse mammary tumor viruses (MTV) integrated at various locations in their DNA. The number and position of these integrants varies from one strain of mouse to another. It has recently been shown that the genomes of many of the MTV code for superantigens. The predicted amino acid sequences of these superantigens and their specificity for TCR V beta differs for each MTV integrant. This study contains the predicted amino acid sequence and V beta specificity of two MTV superantigens that had not previously been analyzed. The results show that both of these MTV superantigens are specific for TCR that bear V beta 7, but unlike the MTV7 superantigen not for receptors bearing V beta 6 or V beta 8.1. The data also support the conclusion of previous studies that the COOH-terminal sequence of these proteins is a major factor in controlling their V beta reactivity.

Amino Acid Sequence↗
PubMed1992

Detection and biochemical characterization of the mouse mammary tumor virus 7 superantigen (Mls-1a).

Mouse mammary tumor viruses encode superantigens that bind to class II major histocompatibility complex proteins and engage T cells that bear particular V beta s. Among these superantigens is the long known, but previously uncharacterized, Mls-1a product, encoded by Mtv-7. Using a monoclonal antibody, we detect the Mtv-7 superantigen on the surface of activated B cells, but not on T cells or resting B cells. The superantigen is synthesized as a 45 kd transmembrane glycoprotein precursor, but is proteolytically processed to yield an 18.5 kd surface protein that we suggest is the functional form of the superantigen.

Animals↗
PubMed1990

Immunological activity of covalently linked T-cell epitopes.

Immune responses to proteins necessarily involve the recognition by T lymphocytes of a peptide or peptides derived from a protein complexed with a major histocompatibility antigen. The T-cell response of BALB/c mice to the bacteriophage lambda cI repressor protein (residues 1-102) is directed predominantly towards the epitope contained within a single peptide encompassing residues 12-26. Similar phenomena of immunodominance of a particular peptide have also been observed in other protein systems. The mechanisms that have been suggested to account for the focusing of the T-cell response are partial deletion in the T-cell repertoire, biased antigen processing, and competition for binding to the presenting molecule, the major histocompatibility complex encoded class II transplantation antigen. In a model system with a polypeptide containing two synthetically linked immunologically active epitopes, we now demonstrate the existence of a hierarchy between these epitopes, so that the immune response elicited is directed mainly towards the more immunogenic epitope, whereas the less immunogenic epitope elicits little or no T-cell reactivity. In addition, the same hierarchy of dominance is also apparent when the polypeptide is used to induce tolerance in the periphery in adult mice. The chimaeric peptide can induce tolerance only towards the more immunogenic epitope. These experiments indicate that the rules governing antigen processing and presentation that result in T-cell activation are apparently the same as the rules that govern the processes resulting in the induction of tolerance.

Animals↗
PubMed1989

Murine MHC polymorphism and T cell specificities.

The major histocompatibility complex (MHC) genes are polymorphic in mouse and man. The products of these genes are receptors for peptides, which while bound, are displayed to T lymphocytes. When bound peptides from antigens are recognized by T lymphocytes, an immune response is initiated against the antigens. This study assessed the relation of the polymorphic MHC molecules to their peptide specificity. The results indicate that although an individual of the species has a limited ability to recognize antigens, the species as a whole has broad reactivity. This rationalizes the extreme polymorphism observed.

Animals↗