Biomedical subjects

D Burstyn

Publications and source records attributed to D Burstyn.

5 recordsLinked to original sources

PubMed1993

Shared T cell-defined antigens on independently derived tumors.

We report that a subset of tumors independently derived from a cloned line of contact-inhibited, non-tumorigenic murine fetal fibroblasts confer cross-protective immunity against each other in vivo. Concordant with the in vivo cross-protection, cytolytic T cell clones from mice immunized with one of these tumor lines specifically lyse the three other lines in the same set but do not cross-react with either the nontumorigenic parental line or another similarly derived tumor line representing a different antigenic profile. This and other recent evidence for shared expression of tumor rejection Ag contrasts with the antigenic diversity previously described for chemical- and radiation-induced tumors. In the interpretation of such data it is essential to distinguish between Ag expressed in association with the transformation process and Ag induced by random mutation of already transformed cells.

Animals↗

PubMed1993

Genetic stability and recombinant product consistency.

A committee of U.S. industry scientists from the Pharmaceutical Manufacturers Association has reviewed the recent suggestions of Galibert and Center for Biologics Evaluation and Research (CBER) regarding assurances of product consistency by cloning and sequencing efforts. We disagree that their proposals will achieve this goal, and estimate that such efforts will be very costly in terms of regulatory agency time examining artifactual errors as well as industry resources. We feel that current analytical and manufacturing technology is adequate to assure recombinant product consistency without the suggested cloning and sequencing measures.

Animals↗

PubMed1992

Major histocompatibility complex determinants select T-cell receptor alpha chain variable region dominance in a peptide-specific response.

Dominant expression of T-cell receptor (TCR) alpha or beta chain variable region (V alpha or V beta) gene families has been observed in the T-cell response to some conventional peptide antigens. Current models for the interaction of TCR V region elements with different determinants of a major histocompatibility complex (MHC)-peptide complex, the normal TCR ligand, suggest that the TCR V-J junctional region (CDR3, where J is joining) is the primary contact with a peptide epitope and that other TCR V region segments may interact directly with neighboring MHC determinants. This suggests that V alpha or V beta dominance in a specific response can be MHC-selected. In this case, if related peptides bind to an MHC molecule in a similar orientation, they could select for identical V alpha or V beta dominance even if they are noncrossreactive at the level of T-cell activation. We have screened for this possibility by introducing minimal conservative substitutions in a synthetic peptide, YYEELLKYYEELLK, that is presented to T cells in association with an uncommon A beta E alpha d mixed Ia isotype. We report here that the peptide variant FFEELLKFFEELLK is noncrossreactive with YYEELLKYYEELLK but appears to preserve the same MHC binding motif since T-cell responses are restricted to the same mixed A beta E alpha isotype. Although the two peptides are noncrossreactive in either direction, the same members of the V alpha 4 gene family are dominantly expressed in T cells specific for either peptide. We conclude that the similar topography of the two MHC-peptide complexes gives functional significance to a unique A beta E alpha determinant that selects for V alpha 4 dominance.

Amino Acid Sequence↗

PubMed1989

Requirements for stimulation of autoreactive T cells by thymic stroma.

Thymic stromal cells are more efficient than similarly treated spleen cells for Ag presentation to Ag-specific, MHC-restricted T cell lines. Thymic stromal cells fail, however, to stimulate proliferation of autoreactive T cell lines. This failure to stimulate autoreactive T cells does not appear to be due to tolerance induction because thymic stroma does not interfere with subsequent stimulation by spleen cells. Moreover, the ability of thymic stromal cells to stimulate autoreactive T cells can be restored by addition of exogenous IL-1. This demonstrates that the specific self-determinants recognized by autoreactive T cells can be expressed on thymic stromal cells. Failure of stimulation by thymic stromal cells in the absence of exogenous IL-1 may reflect a difference in the physiologic requirements for activation of autoreactive T cells as compared to Ag-specific, MHC-restricted T cells.

Animals↗

PubMed1989

Autoreactive T-cell response to resting or activated B cells.

Cloned autoreactive T-cell lines and hybridomas have been selected in many laboratories. A number of observations have suggested that activation of Ia-positive stimulators may be required for optimal induction of an autoreactive response. We have examined the ability of small resting B cells fractionated by centrifugal elutriation to stimulate the proliferative response of seven cloned autoreactive T-cell lines. Of these, six were efficiently stimulated by resting B cells. One I-Ed-specific Th2-type T-cell clone failed to be stimulated by resting B cells. This clone did, however, respond to this same cell fraction following lipopolysaccharide (LPS) activation. An independent I-E-specific Th2 clone was stimulated by resting B cells. It appears, therefore, that a requirement for activated stimulators is not a general property of either autoreactive T cells or the Th2 helper T-cell subset.

Animals↗