Biomedical subjects

C Labadie

Publications and source records attributed to C Labadie.

3 recordsLinked to original sources

PubMed1997

Tolerance to p53 by A2.1-restricted cytotoxic T lymphocytes.

Elevated levels of the p53 protein occur in approximately 50% of human malignancies, which makes it an excellent target for a broad-spectrum T cell immunotherapy of cancer. A major barrier to the design of p53-specific immunotherapeutics and vaccines, however, is the possibility that T cells may be tolerant of antigens derived from wild-type p53 due to its low level of expression in normal thymus and lymphohemopoetic cells. The combination of p53 deficient (p53-/-) and p53+/+ HLA-A2.1/Kb transgenic mice was used as a model to explore the possibility that A2.1-restricted cytotoxic T lymphocytes (CTL) are functionally tolerant of self peptides derived from the wild-type p53 tumor suppressor protein. A2.1-restricted CTL specific for a naturally processed p53 self-epitope spanning residues 187-197 were completely aborted in p53+/+ as opposed to p53-/- transgenic mice. In contrast, CTL specific for a second self-epitope spanning residues 261-269 of the murine p53 sequence were detected in both p53-/- and p53+/+ A2.1/Kb transgenic mice. However, the avidity of the CTL effectors obtained from p53+/+ mice was 10-fold lower than that obtained from p53-/- mice, again suggesting elimination of CTL with high avidity for the A2.1-peptide complex. The circumvention of functional tolerance of high avidity CTL may therefore be a necessary prerequisite for optimizing immunotherapy against A2.1-restricted wild-type p53 epitopes in humans.

Animals↗

PubMed1997

Identification of Her-2/Neu CTL epitopes using double transgenic mice expressing HLA-A2.1 and human CD.8.

The Her-2/neu protooncogene is associated with malignant transformation and aggressive disease. Because of its overexpression in tumor cells and because it has been shown to be immunogenic, this protein represents an excellent target for T-cell immunotherapy. By identifying potential HLA-A2.1-binding peptides from the Her-2/neu sequence, peptides were selected as candidate T-cell epitopes. The immunogenicity of each peptide was evaluated by priming double transgenic mice expressing both the human (hu) CD8 and HLA-A2.1 molecules with synthetic peptides corresponding to these sequences. Because of the lack of interaction between murine CD8 and HLA-A2.1, expression of huCD8 on murine cells facilitates recognition of HLA molecules on human tumor cell lines. This led to the identification of two peptides that elicit an A2-restricted CTL response, one of which has not been previously identified. Both peptide-specific CTL populations were able to specifically lyse A2.1 and Her-2/neu expressing human tumor cells originating from a variety of tissues, demonstrating the utility of this murine model in identifying peptides presented by human cells. However, several Her-2/neu peptides previously reported to be immunogenic for human CTL were found not to be immunogenic in transgenic mice. The basis for these discrepancies is discussed.

Amino Acid Sequence↗

PubMed1994

Relaxographic imaging.

A fundamental extension of NMR imaging is described. The distribution of relaxation times, the relaxogram, is considered as the third (or fourth) dimension of a set of 2D (or 3D) image data. There is a relaxographic dimension for each type of relaxation: longitudinal, transverse, rotating frame, etc. It is the formal inverse Laplace transform of the relaxation decay data set. Thus, combined relaxography and imaging (CRI) approaches are defined. CRI data can be displayed in two fundamental ways: localized relaxograms (relaxograms from any part of an image) or relaxographic images (images produced from discrete portions of a relaxogram). Relaxographic images are elemental components of the true spin-density image. The CRI concept is demonstrated with longitudinal relaxation data from samples of yeast cells suspended in media containing the contrast agent (CR) GdDTPA2-. This allows the discrimination of subvoxel intra- and extracellular 1H2O signals in the relaxograms from very small image voxels (about 400 nl). It is possible to isolate the intracellular 1H2O resonance from as few as a million cells. Relaxographic images are shown of the extracellular space (i.e., the distribution space of the CR) and the cytoplasmic space of a cell suspension with a cytocrit gradient. These have important potential applications in the in vivo situation. Also, the extent of equilibrium transcytolemmal water exchange can be detected and quantified.

Body Water↗