Human CD28 and CTLA-4 Ig superfamily genes are located on chromosome 2 at bands q33–q34

CD28 is a cell surface molecule present on most peripheral T cells which has been implied in the amplification of the T-cell response in vitro. Using in situ hybridization on human prometaphase cells, we have found that the human CD28 gene maps to chromosome 2 at bands q33–q34, as shown previously for the CTLA-4 gene. CD28 and CTLA-4 are both members of the Ig superfamily, where they define a subgroup of membrane-bound single V domains. Their chromosomal proximity and their close structural relationship suggest that these two genes could be the result of the duplication of a common evolutionary precursor and may share some functional properties. Address correspondence and offprint requests to: M. Lafage-Pochitaloff.     

GENETICS OF SORDARIA FIMICOLA. IX. LINKAGE GROUP II

Ten mutant sites have been located in linkage group II of Sordaria fimicola, nine of them affecting fertility. Two different regions of the chromosome are marked with allelic mutations or mutant sites in closely linked loci involved in sexual reproduction. Mutants of one of these two regions also have an arginine deficiency. Crosses between the self-sterile mutants of each region yield hybrid perithecia containing asci with four spores of each parental genotype and few or no asci with recombinant spores. The bearing that these findings have upon the evolution of heterothallism is discussed.     

T-cell: section report

The antibodies submitted to the T-cell section were evaluated by different laboratories. We focused our studies on antibodies that reacted to defined molecules to the CD28 family and their ligands B7/butyrophilin family.     

Growth of V79 cells as xenograft tumors promotes multicellular resistance but does not increase spontaneous or radiation-induced mutant frequency

A Chinese hamster V79 xenograft model was developed to determine whether cells subjected to a hypoxic tumor microenvironment would be more likely to undergo mutation at the HPRT locus. V79-171b cells stably transfected with VEGF and EGFP were grown subcutaneously in immunodeficient NOD/ SCID mice. V79-VE tumors were characterized for host cell infiltration, doubling time, hypoxic fraction, vascular perfusion, and response to ionizing radiation. When irradiated in vitro, the mutant frequency for a given surviving fraction did not differ for cells grown in vivo or in vitro. Similar results were obtained using HCT116 human colorectal carcinoma cells grown as xenografts. However, V79-VE cells grown as xenografts were significantly more resistant to killing than monolayers. The background mutant frequency and the radiation-induced mutant frequency did not differ for tumor cells close to or distant from blood vessels. Similarly, tumor cells from well-perfused regions showed the same rate of strand break rejoining and the same rate of loss of phosphorylated histone H2AX as cells sorted from poorly perfused regions. Therefore, deleterious effects of the tumor microenvironment on DNA repair efficiency or mutation induction could not be demonstrated in these tumors. Rather, development of multicellular resistance in V79-VE tumors acted to reduce mutant frequency for a given dose of radiation.     

Interaction between photoperiod and an endogenous seasonal factor in influencing the diel locomotor activity of the benthic polychaete Nereis virens Sars

The locomotor activity of Nereis virens Sars associated with food prospecting was investigated in response to photoperiod and season using an actograph. Experimental animals which had been reared under natural photoperiods were exposed to two constant photoperiodic treatments, LD 16:8 and LD 8:16, in both the autumn and winter and in the absence of tidal entrainment. Autocorrelation analysis of rhythmicity showed that during the autumn, animals under the LD 16:8 photoperiod displayed a strong nocturnal rhythm of activity, whereas animals under the LD 8:16 photoperiod showed only a weak nocturnal activity rhythm. This is believed to represent an autumn feeding cessation that is triggered when the animals pass through a critical photoperiod LD(crit) <12:>12. Later in the winter, however, animals exposed to both photoperiodic treatments showed strong rhythms of foraging activity irrespective of the imposed photoperiod. It is suggested that the autumn cessation may maximize the fitness of N. virens, a spring-breeding semelparous organism, by reducing risk during gamete maturation, while spontaneous resurgence of activity after the winter solstice permits animals that are not physiologically competent to spawn to accrue further metabolic reserves. This response is believed to be initiated by a seasonal (possibly circannual) endogenous oscillator or interval timer.     

Hypertonic saline enhances expression of phosphorylated histone H2AX after irradiation

Phosphorylation of histone H2AX at serine 139 occurs at sites surrounding DNA double-strand breaks, producing discrete spots called "foci" that are visible with a microscope after antibody staining. This modification is believed to create changes in chromatin structure and assemble various repair proteins at sites of DNA damage. To examine the role of chromatin structure, human SiHa cells were exposed to hypertonic salt solutions that are known to condense chromatin and sensitize cells to chromosome damage and killing by ionizing radiation. Postirradiation incubation in 0.5 M Na(+) increased gammaH2AX expression about fourfold as measured by flow cytometry and immunoblotting, and loss of gammaH2AX was inhibited in the presence of high salt. Focus size rather than the number of radiation-induced gammaH2AX foci was also increased about fourfold. When high-salt treatment was delayed for 1 h after irradiation, effects on focus size and retention were reduced. The increase in focus size was associated with a decrease in the rate of rejoining of double-strand breaks as measured using the neutral comet assay. We conclude that gammaH2AX expression after irradiation is sensitive to salt-induced changes in chromatin structure during focus formation, and that a large focus size may be an indication of a reduced ability to repair DNA damage.     

Comparative immunological properties of enantiomeric peptides

Summary The immunogenicity of a peptide composed of only d-amino acids is compared with that of the corresponding l-peptide enantiomer. Following three administrations of 100 g of individual peptide formulated with different adjuvants (Freund's complete adjuvant, QS21, or alum) to BALB/c mice, guinea pigs and rabbits, the l-peptide elicited strong l-peptide-specific IgG antibody responses in all formulations, whereas the d-peptide-induced d-peptide-specific IgG antibodies in the Freund's complete adjuvant and QS21 formulations, but was nonimmunogenic in the alum formulation. Mouse T-cell lines induced by the d-peptide formulated in Freund's complete adjuvant were found to express significant amounts of IL-2 when they were stimulated by the d-peptide. When an equal amount of both enantiomers was mixed and administered in Freund's complete adjuvant, only an l-peptide-specific IgG antibody response was observed. These results suggest that (i) d-peptide is immunogenic when strong adjuvant is provided; (ii) the immune system has preferential recognition of l-amino acid peptide; and (iii) the d-peptide can elicit d-peptide-specific T-cell responses.