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Biomedical subjects

P A Reid

Publications and source records attributed to P A Reid.

10 recordsLinked to original sources
PubMed1997

The antigen receptors on mature and immature T lymphocytes are coupled to phosphatidylcholine-specific phospholipase D activation.

Phosphatidylcholine-phospholipase D has been proposed to play a key role in the transduction of the proliferative responses of a wide range of mitogens and growth factors. We now report that the antigen receptors on T lymphocytes derived from human tonsillar or murine splenic preparations are coupled to phosphatidylcholine (PtdCho)-phospholipase D (PLD) activation following stimulation of these T cells with anti-CD3 antibodies. However, since we also demonstrate that the antigen receptors on murine thymocytes are coupled to PtdCho-PLD activation, we propose that it is unlikely that this PLD pathway plays a central role in the transduction of T-cell proliferative responses, but rather, may be involved in either driving cells into cycle or maintaining cell cycle progression, processes required both for proliferation and activation-induced cell death. Whilst the molecular mechanisms underlying T-cell receptor (TCR)-coupling to PtdCho-PLD activation in these cells have not been fully defined, kinetics studies and experiments using pharmacological inhibitors of protein tyrosine phosphatases (PTPases) and reconstituting CD3-coupled PtdCho-PLD activity in streptolysin-O permeabilized cells, suggest that the TCR/CD3 complex, under optimal conditions of activation, may be predominantly coupled to PtdCho-PLD activation downstream of tyrosine phosphorylation of phospholipase C-gamma (PLC-gamma), phosphatidylinositol (PtdIns)P2 hydrolysis, calcium mobilization and protein kinase C (PKC) activation.

Animals↗
PubMed1996

Breast cancer worry and screening: some prospective data.

Breast cancer concerns were measured among 353 women, ages 40-75, from North Dakota. One year later, participants were recontacted and asked about their screening behavior during the previous year. Greater concern about breast cancer, even the highest level of concern, was related to a higher likelihood that women performed breast self-examination, had a mammography screening, and had a clinical breast examination. These data do not support the idea that worry inhibits action; instead, they suggest that nonpathological worry motivates self-protective behavior.

Adult↗
PubMed1992

Irreversible association of peptides with class II MHC molecules in living cells.

Functional, morphological and biochemical evidence indicates that class II major histocompatibility complex (MHC) molecules associate with processed peptides during biosynthesis. Peptide/MHC complexes in living cells have been reported to be less stable than similar complexes generated in vitro, which has led to the suggestion that there may be a peptide exchange mechanism operating in vivo. Although this could increase the capacity for binding incoming antigens, it would reduce the efficacy of processed antigenic peptides by exchanging these for self peptides. Here we measure the half-life of peptide/class II complexes in human antigen-presenting cells and find that it is very similar to the half-life of class II molecules themselves, indicating that peptides are bound irreversibly under physiological conditions. Thus class II MHC retains long-term 'memory' of past encounters with antigen to maximize the opportunity for T cell/antigen-presenting cell interaction.

Antigen-Presenting Cells↗
PubMed1992

Constitutive endocytosis and recycling of major histocompatibility complex class II glycoproteins in human B-lymphoblastoid cells.

Cleavable cell surface radiolabelling reagents were used to measure the endocytosis and recycling of class II major histocompatibility complex (MHC) glycoproteins in human B-lymphoblastoid cells. It is shown that mature class II alpha beta dimers on the cell surface are constitutively endocytosed and that recycling can be demonstrated even from small endosomal pools. Endocytosis was blocked when cellular ATP levels were depleted or when clathrin polymerization was inhibited, implicating clathrin-coated pits in the endocytic process. Taken together with earlier studies, these results suggest that mature class II MHC molecules are constitutively endocytosed and recycled from acidic peripheral endosomes which may enhance their capacity to bind and present T cell epitopes which do not require processing.

Adenosine Triphosphate↗
PubMed1991

Processed antigen binds to newly synthesized MHC class II molecules in antigen-specific B lymphocytes.

We describe the direct detection of radiolabeled antigen fragments bound to class II MHC molecules following immunoglobulin-mediated endocytosis and processing of native antigen in B lymphoblastoid cells. Tris-Tricine SDS gels revealed six distinct iodinated processing products that could be detected on class II MHC 1 hr after antigen endocytosis and persisted for at least 20 hr. These physiological processed antigen-class II complexes were remarkably stable, as judged by the fact that class II alpha beta dimers, which remain associated in SDS, became labeled with the same set of processed peptides. Using a lectin-binding assay, we show that these physiological processing products bind to the newly maturing population of MHC molecules rather than binding to the preexisting cell surface population; in contrast, an exogenous peptide binds predominantly to the latter population. A direct T cell-independent assay for processed peptide-MHC complex formation should facilitate additional studies on the exogenous antigen processing pathway.

Antibodies, Monoclonal↗
PubMed1990

Cycling of cell-surface MHC glycoproteins through primaquine-sensitive intracellular compartments.

Class II major histocompatibility complex (MHC) glycoproteins associate with peptides derived from material endocytosed by antigen-presenting cells and processed along the endocytotic pathway. No consensus exists as to what extent class II molecules themselves are endocytosed and it is not known whether endocytosed MHC class II molecules can be recycled again to the cell surface--an itinerary which might allow a single cell-surface MHC molecule to associate with different peptides during its lifetime. We now show by using new cleavable labelling reagents that class II and class I MHC on B lymphoblastoid cells are continually endocytosed and recycled to the cell surface. The intracellular pool size is normally kept small by efficient recycling, but in the presence of primaquine the rate of recycling is slowed, thereby increasing the size of this pool substantially. On removal of the amine, the intracellular population recycles rapidly to restore the original distribution. These results reveal a cycle that might explain the rapid binding and turnover of some peptide/class II MHC complexes and the exchange of pre-existing for new peptides observed in living cells.

Antibodies, Monoclonal↗
PubMed1990

The antigen processing pathway in B lymphocytes.

Monovalent antigen bound to membrane immunoglobulin on human B lymphoblastoid cells is endocytosed through coated pits and passes sequentially from a site which actively recycles membrane to the cell surface and then to a proteolytically active processing site. A high affinity of immunoglobulin for antigen precludes antigen dissociation following endocytosis and results in the processing of an antigen/Ig complex yielding an epitope-specific pattern of processing. Processing of the immunoglobulin also occurs and is enhanced by occupancy with monovalent antigen.

Antigens↗