Search PubMed⌕ Search

Biomedical subjects

Peter E Jensen

Publications and source records attributed to Peter E Jensen.

26 records · Page 2Linked to original sources
PubMed2003

HLA-DO. A useful marker to distinguish florid follicular hyperplasia from follicular lymphoma by flow cytometry.

HLA-DO expression is regulated during B-cell development and activation. To determine whether the level of HLA-DO expression is a helpful marker in the differential diagnosis between florid follicular hyperplasia and follicular lymphoma, we analyzed single-cell suspensions from 29 lymph node specimens by 4-color flow cytometry. Of the 29 specimens, 7 were from patients with florid follicular hyperplasia, in which the clonality of the germinal center B cells (GCBCs) was indeterminate by flow cytometric immunophenotyping. The remaining 22 cases were follicular lymphomas; neoplastic cells in 2 of these cases lacked expression of surface immunoglobulin light chains. The level of HLA-DO expression in the reactive CD10+ GCBCs in florid follicular hyperplasia was markedly down-regulated compared with the CD10- polytypic B cells of the same specimens. In contrast, the level of HLA-DO expression in the CD10+ neoplastic cells in all cases of follicular lymphomas was similar to that of the CD10- polytypic B cells, thus higher than the reactive CD10+ GCBCs. This difference was confirmed by immunohistochemical staining. Our results suggest that HLA-DO is a useful marker to differentiate florid follicular hyperplasia from follicular lymphoma by flow cytometry, particularly when clonality of the CD10+ B cells is in question.

B-Lymphocytes↗
PubMed2002

Peptide-independent folding and CD8 alpha alpha binding by the nonclassical class I molecule, thymic leukemia antigen.

The nonclassical class I molecule, thymic leukemia (TL), has been shown to be expressed on intestinal epithelial cells and to interact with CD8(+) intraepithelial T lymphocytes. We generated recombinant soluble TL (T18(d)) H chains in bacteria as inclusion bodies and refolded them with beta(2)-microglobulin in the presence or absence of a random peptide library. Using a mAb, HD168, that recognizes a conformational epitope on native TL molecules, we observed that protein folds efficiently in the absence of peptide. Circular dichroism analysis demonstrated that TL molecules have structural features similar to classical class I molecules. Moreover, thermal denaturation experiments indicated that the melting temperature for peptide-free TL is similar to values reported previously for conventional class I-peptide complexes. Our results also show that CD8alphaalpha binding is not dependent on either TL-associated peptide or TL glycosylation.

Animals↗
PubMed2002

Regulated expression of human histocompatibility leukocyte antigen (HLA)-DO during antigen-dependent and antigen-independent phases of B cell development.

Human histocompatibility leukocyte antigen (HLA)-DO, a lysosomal resident major histocompatibility complex class II molecule expressed in B cells, has previously been shown to be a negative regulator of HLA-DM peptide loading function. We analyze the expression of DO in human peripheral blood, lymph node, tonsil, and bone marrow to determine if DO expression is modulated in the physiological setting. B cells, but not monocytes or monocyte-derived dendritic cells, are observed to express this protein. Preclearing experiments demonstrate that approximately 50% of HLA-DM is bound to DO in peripheral blood B cells. HLA-DM and HLA-DR expression is demonstrated early in B cell development, beginning at the pro-B stage in adult human bone marrow. In contrast, DO expression is initiated only after B cell development is complete. In all situations, there is a striking correlation between intracellular DO expression and cell surface class II-associated invariant chain peptide expression, which suggests that DO substantially inhibits DM function in primary human B cells. We report that the expression of DO is markedly downmodulated in human germinal center B cells. Modulation of DO expression may provide a mechanism to regulate peptide loading activity and antigen presentation by B cells during the development of humoral immune responses.

Adult↗
PubMed2002

Class II transactivator is required for maximal expression of HLA-DOB in B cells.

HLA-DO, encoded by the HLA-DOA and HLA-DOB genes, has been shown to function as a modulator of Ag presentation. DNA microarray comparisons between B cells wild-type and mutant for the master regulator of MHC class II transcription, class II transactivator (CIITA), identified HLA-DOA and HLA-DOB as being up-regulated by CIITA. Although HLA-DOA had been shown previously to be regulated by CIITA, HLA-DOB expression was suggested to be independent of CIITA. A series of assays including quantitative RT-PCR, promoter-reporter assays, chromatin immunoprecipitations, and intracellular staining were performed to corroborate the DNA microarray analysis. The combined data demonstrate that HLA-DOB levels are increased by CIITA, and that this difference has an impact on the overall level of HLA-DO expression. Additionally, unlike the classical MHC class II genes, HLA-DOB expression was present in the absence of CIITA, indicating that additional factors mediate HLA-DOB expression in B cells.

Amino Acid Sequence↗
PubMed2002

CD94-NKG2A receptors regulate antiviral CD8(+) T cell responses.

CD8(+) T lymphocytes mediate immunosurveillance against persistent virus infections and virus-induced neoplasia. Polyoma virus, a highly oncogenic natural mouse DNA virus, establishes persistent infection, but only a few mice are highly susceptible to tumors induced by the virus. Mature antiviral CD8(+) T cells expand in tumor-susceptible mice, but their cytotoxic effector activity is nonfunctional in vivo. Here we show that the natural killer cell inhibitory receptor, CD94-NKG2A, is up-regulated by antiviral CD8(+) T cells during acute polyoma infection and is responsible for down-regulating their antigen-specific cytotoxicity during both viral clearance and virus-induced oncogenesis.

Animals↗
PubMed2002

Analysis of two acidic P6 pocket residues in the pH dependency of peptide binding by I-E(k).

Peptide binding to major histocompatibility complex (MHC) class II molecules is optimal at mildly acidic pH. X-ray crystal structures solved for the murine class II molecule I-E(k) revealed an interesting localization of negatively charged residues within the P6 pocket, which may have implications in the pH dependency of peptide binding. Protonation of these critical residues, under acidic conditions, has been proposed to be important for the formation of stable class II-peptide complexes. In this study, we address a possible role for these charged residues in the pH dependency of peptide binding. An I-E(k) mutant was generated in which two acidic residues of the P6 pocket were substituted with uncharged residues. This class II mutant was expressed, purified, and tested for its ability to bind peptides. The mutant I-E(k) was observed to load peptides optimally at mildly acidic pH. Peptide binding to the mutant was enhanced in the presence of DM, and optimal DM-enhanced binding occurred in the acidic pH range. These findings indicate that structural changes other than protonation of acidic residues in pocket 6 must play a dominant role in pH-regulated peptide binding to I-E(k).

Animals↗
PubMed2002

Positive selection of a Qa-1-restricted T cell receptor with specificity for insulin.

The phenotype and development of T cells from transgenic mice expressing a T cell receptor with specificity for insulin presented by the MHC class Ib molecule Qa-1(b) was investigated. Peripheral T cells from the transgenic mice express CD8 and, after activation, kill Qa-1(b)-positive lymphoid target cells in the presence of soluble insulin. Thymic selection requires expression of Qa-1(b) but not the dominant Qa-1-associated peptide, Qdm. In contrast to conventional T cells, selection is at least as efficient when the selecting ligand is expressed only on hematopoietic lineage cells as compared to expression on epithelial cells in the thymus. Our findings suggest that there is a dedicated population of Qa-1-restricted T cells that are selected by interaction with Qa-1 and that the cellular requirements for selection may differ from conventional T cells.

Animals↗