Tumor Suppressor Gene-Derived Peptide Antigens

Foreign and self endogenous proteins can be processed and presented as peptides bound to class I and II MHC to CD8 or CD4-positive T cells. In the case of mutant tumor suppressor proteins, proteosomal processing of the mutant protein could occur either in the tumor cell or in an antigen-presenting cell to generate a variety of peptides that can be transported into the endoplasmic reticulum and loaded on the MHC. These peptides may induce tumor suppressor specific T cells in the presence of sufficient T help and costimulation. In human cancer, p53 is frequently found to be both somatically mutant and overexpressed. We and others are currently investigating the potential of peptide-induced cellular immunotherapy to induce cytotoxic T cells to peptides containing point mutant p53, or other oncogene products, thus potentially inducing tumor-specific cellular immunity. There are many potential prerequisites for successful immunotherapeutic targeting of intracellular antigens such as p53, including: (1) the protein must have a sufficient expression level; (2) it should be a candidate for proteolytic degradation and transport into the ER; (3) the tumor-specific epitope must have adequate affinity to the corresponding MHC restriction element; (4) the MHC complex must be expressed at sufficient levels on the cell surface to make the tumor-specific epitope accessible to T cells; and (5) the method of therapeutic immunization must effectively induce oncopeptide-specific cytotoxic T lymphocytes.     

Recent coral facies of the Indian Ocean Coast of Somalia with an interim check list of corals

Summary From a study of two areas, Jesira and the Bajuni Archipelago, about 400 km apart, a general pattern can be established for the Recent facies, together with the morphological and taxonomic features of the corals. Present day coral development is characterized by true fringing reefs in the Bajuni Archipelago and by scattered patches and knolls in the Jesira area. The coral fauna, consisting of 27 genera and 63 species so far (including all uncertainties, but not sight records), is rather poor, though coral communities are locally well developed. These figures probably reflect incomplete study and sampling. Although comparison with other areas may therefore be premature, a preliminary biogeographical analysis suggests that this fauna is more closely related to that of the Red Sea than to East Africa and the Seychelles. This differs from other published biogeographical work on Indian Ocean coral faunas, but further study of the corals in this and neighbouring areas of the Indian Ocean is needed in order to resolve this apparent anomaly.     

Simian virus 40 small-t antigen stimulates viral DNA replication in permissive monkey cells.

The simian virus 40 (SV40) large-T antigen is essential for SV40 DNA replication and for late viral gene expression, but the role of the SV40 small-t antigen in these processes is still unclear. We have previously demonstrated that small t inhibits SV40 DNA replication in vitro. In this study, we investigated the effect of small t on SV40 replication in cultured cells. CV1 monkey cell infection experiments indicated that mutant viruses that lack small t replicate less efficiently than the wild-type virus. We next microinjected CV1 cells with SV40 DNA with and without purified small-t protein and analyzed viral DNA replication efficiency by Southern blotting. Replication of either wild-type SV40 or small-t deletion mutant DNA was increased three- to fivefold in cells coinjected with purified small t. Thus, in contrast to our in vitro observation, small t stimulated viral DNA replication in vivo. This result suggests that small t has cellular effects that are not detectable in a reconstituted in vitro replication system. We also found that small t stimulated progression of permissive monkey cells--but not of nonpermissive rodent cells--from G0-G1 to the S phase of the cell cycle, possibly leading to an optimal intracellular environment for viral replication.     

Malignant tumours in patients with HIV infection.

One of the most important though somewhat neglected aspects of research in HIV infection concerns the development, clinicopathological characteristics, and treatment of malignant tumours in infected patients. With the improved survival of patients with AIDS owing to the better prevention and treatment of infectious complications there may well be an increase in AIDS related malignancies. This paper reviews the epidemiology, pathology, and treatment of malignant tumours in patients with HIV.     

An MspI polymorphism in the X-specific region proximal to the pseudoautosomal boundary. A new example of a unique “African” marker?

A polymorphic MspI site was located in the X-specific region proximal to the pseudoautosomal boundary. Two alleles defined by the absence or the presence of the MspI site were detected by the polymerase chain reaction (PCR) in a sample of Bantu-speaking individuals from Cameroon. No variation for this site was observed in a population sample from Italy.     

Screening for point mutations in exon 10 of the low density lipoprotein receptor gene by analysis of single-strand conformation polymorphisms: detection of a nonsense mutation — FH469→Stop

DNA from 40 unrelated familial hypercholesterolemia (FH) heterozygotes were subjected to analyses of single-strand conformation polymorphisms (SSCPs) of exon 10 of the low density lipoprotein receptor (LDLR) gene. Four different SSCP patterns were observed. The underlying mutations were characterized by DNA sequencing. Three of the patterns represented the three genotypes of a recently described sense mutation in codon 450. A method based upon the polymerase chain reaction (PCR) was developed to analyze this mutation. The frequencies of the wild-type (G at nucleotide 1413) and mutant (A at nucleotide 1413) alleles were 0.56 and 0.44, respectively. The fourth pattern was found in only one FH heterozygote and was caused by heterozygosity at nucleotide 1469 (G/A). Nucleotide 1469 is the second base of codon 469_Trp(TGG). The GA mutation changes this codon into the amber stop codon, and is referred to as FH_469Stop. The mutant receptor consists of the amino terminal 468 amino acids. Because the truncated receptor has lost the membrane-spanning domain, it will not be anchored in the cell membrane. FH_469Stop destroys an AvaII restriction site, and this characteristic was used to develop a PCR method to establish its frequency in Norwegian FH subjects. Two out of 204 (1%) unrelated FH heterozygotes possessed the mutation.     

Oxyprenylated secondary metabolites: a survey of their innovative extraction methodologies

Phytochemistry Reviews - Oxyprenylated secondary metabolites of plant, fungal, and microbial origin have emerged as biologically active natural compounds with a great potential for the next future....     

Characterization of diverse primary herpes simplex virus type 1 gB-specific cytotoxic T-cell response showing a preferential V beta bias.

The glycoprotein B (gB) from herpes simplex virus type I is a major target of cytotoxic T lymphocytes (CTL) in C57BL/6 mice. The majority of these T cells are directed to a single Kb-restricted determinant, gB498-505. We have analyzed the T-cell receptor (TCR) usage in gB-specific CTL lines derived shortly after virus infection. The CTL populations preferentially used two V beta regions, a dominant V beta 10 element and a subdominant V beta 8 element. Detailed sequence analysis revealed considerable TCR beta-chain heterogeneity despite a striking level of predicted amino acid conservation at the V beta-D beta junction. This junction forms part of the third hypervariable loop of the TCR thought to directly contact the major histocompatibility complex-bound antigenic peptide. The results reveal considerable diversity within the primary T cells responding to a single viral determinant while still maintaining a high degree of TCR V beta bias and sequence conservation at the V-D-J junction.     

Regulatory action of prolactin on the in vitro growth of CD34+ve human hemopoietic progenitor cells

The pituitary hormone prolactin (Prl) is known to act as a local regulator of immune cell function, and Prl-binding receptors (Prl-R) have been described to share distinctive features with the members of the newly described cytokine/hemopoietin receptor superfamily. Here we show that the hormone can functionally interact with lineage-specific hemopoietic factors. When highly purified progenitor cells (CD34+ve) were seeded in semisolid methylcellulose cultures in the presence of interleukin (IL)-3, granulocyte-macrophage colony stimulating factor (GM-CSF), and erythropoietin (Epo), a selective enhancing effect of Prl on the formation of colony forming unit-granulocyte (CFU-G) and burst forming unit-erythroid (BFU-E) colonies was observed. The effect of the hormone was plotted as a bell shaped curve, with the optimal response at the supraphysiological concentration of 50 ng/ml. Limiting dilution analysis showed that Prl acted directly on hemopoietic progenitors. This was confirmed by the observation on the CD34+ve cells of Prl-binding sites reacting with the specific monoclonal antibodies (mAbs), U5 and PrR-7A. Immunoprecipitation of the metabolically labeled CD34+ve cells with the PrR-7A mAb revealed a structure of 43 kD under reducing conditions. Analysis of the early events associated with the Prl/Prl-R interaction showed an increased number of cells engaged in DNA and hemoglobin synthesis. Enhanced erythroid differentiation of CD34+ve cells in the presence of Prl was secondary to upmodulation of receptors for the lineage-specific factor Epo. Together these data demonstrate the existence of a functional interplay between Prl. and hemopoietic factors. © 1995 Wiley-Liss, Inc.