The Tla locus: a new allele and antigenic specificity.

Four of 23 H-2 alloantisera screened for anti-TL activity contained such activity. One of these alloantisera, D-35, defined a new TL specificity, TL.5, and a new Tla allele, Tlad. TL.5 has all the characteristics of a TL antigen and has a different strain distribution than previously known ones. This new complexity at the Tla locus and the previous finding of other serologically defined genes in the Tla region indicate that this genetic region cannot be ignored in analyzing antisera produced in strains made congenic for the major histocompatibility complex.     

Polymorphism and diversity in the Tla gene system

The TL products of mouse strains carrying the Tla ^a, Tla^a, and Tla ^e haplotypes were analyzed by comparative peptide mapping. As expected from their known serologic differences, TL antigens from strain A (Tla ^a), A.CA strain (Tla ^d) and P/J strain (Tla ^e) mice showed structural variation. However, comparable variations were also observed in the TL product derived from strains expressing the serologically indistinguishable Tla ^a allele (A, NFS/N, SJL/J, C57BR, and C58) demonstrating additional unexpected polymorphism in the TL system. When compared with the structural diversity of the H-2 K and D gene products, the structural variation of the TL antigens was small. Taken together, the results of our analysis of the TL products suggest that Tla polymorphism is more extensive than previously thought; however, the structural diversity of the products is still low compared with K and D gene products.     

Genomic organization of the mouse Tla locus: study of an endogenous retrovirus-like locus reveals polymorphisms related to different Tla haplotypes

A retrovirus element (TLev1) is located within the Thymus leukemia antigen (T7a) locus of the C57BL/10 mouse major histocompatibility complex. Low-copy probes have been isolated from sequences flanking the TLev1 integration site to examine the distribution of TLev1 among inbred mouse strains having genotypically determined variations in TL-antigen expression. It was found that the low-copy probes cross-hybridize to regions within the Tla locus in a genotype-specific manner. Although a strong association was found between TL mouse strains and TLev1, the presence or absence of the TLev1 locus did not exclusively correlate with expression or nonexpression of TL antigens. Analysis of different Mus subspecies indicates that TLev1 integrated into a common ancestor of the species Mus musculus. It is suggested that the loss of the TLev1 locus from certain mouse genomes reflects evolutionary rearrangements in the TL region; the resulting diversity may relate to the differential expression of TL antigens among mouse strains. The probes described here provide a useful tool for examining the genomic expansions and contractions which have occurred during the evolution of the Tla locus     

Further polymorphism of the Tla locus defined by monoclonal TL antibodies

Six new monoclonal TL antibodies are described. At least one new TL antigen is defined (TL.7), and at least one more Tla allele, bringing the total number of known Tla alleles to six. Five of the monoclonal antibodies, and probably all six, identify distinct TL antigenic specificities. Four of these antigens conform in strain distribution and expression on leukemia cells to antigens defined by conventional antisera. The data contain a hint that monoclonal TL antibodies like TL.m6 may serve to identify a region of the Tla gene, which determines whether or not prothymocytes will respond to physiological induction by expressing TL, and thus may provide a means to study the regulatory mechanism that determines whether mouse strains are phenotypically TL⁺ or TL^– The nomenclature TL.m4–9 for the six monoclonal antibodies described follows McIntyre and coworkers (1980). The serial numbers 4–9 do not imply any correspondence with numbers assigned to TL antigens defined by conventional antisera. The corresponding hybridoma lines are available to interested investigators.     

The evolution of molecular biology into systems biology

Systems analysis has historically been performed in many areas of biology, including ecology, developmental biology and immunology. More recently, the genomics revolution has catapulted molecular biology into the realm of systems biology. In unicellular organisms and well-defined cell lines of higher organisms, systems approaches are making definitive strides toward scientific understanding and biotechnological applications. We argue here that two distinct lines of inquiry in molecular biology have converged to form contemporary systems biology.     

The biology of endotoxin

Endotoxin (lipopolysaccharide, LPS) is the major component of the outer leaflet of Gram-negative bacteria and has profound immunostimulatory and inflammatory capacity. The septic shock syndrome caused by endotoxin still has an unacceptably high mortality rate and, owing to increasing numbers of resistant strains, remains an ongoing threat throughout the world. However, the past years have provided new insights especially into the receptors of the innate immune system that are involved into the recognition of LPS and the initial signal transduction pathways that are engaged after the primary recognition on the cell surface. The knowledge about the molecular basis for the responses to endotoxin may eventually lead to the development of new drugs to fight the fatal effects of bacterial infections.     

The geometrization of biology

The twentieth century has witnessed a geometrization of physics, that is, a reduction of the basic concepts of physics to geometric concepts. The topological approach to biology, recently proposed and to some extent developed by the author, is a small step in the direction of geometrization of biology, but is unable to achieve the main purpose of such a geometrization of biology, namely, the reduction to geometric concepts of such purely biological concepts as ingestion, digestion, assimilation, etc. To achieve this purpose we must find geometric structures or spaces, in which different geometric properties stand to each other in the same formal logical relation, as the different concepts of biology stand to each other. If this were possible, then a set of geometric theorems could be “translated” by an appropriate “glossary” into a set of biological laws. While not offering a solution to this problem, the present paper illustrates the possibility of such an approach on several examples. Certain new types of topological spaces are introduced, which are used for illustration purposes only. It is shown, however, how from a theorem about such spaces a verifiable biological prediction could be made, if these spaces were to be taken seriously. A possible application to biology of E. Artin's theory of braids is outlined.     

The biology of ophiobolins

This review article aims at summarizing the research findings on the biological aspects of ophiobolins, phytotoxins produced by the pathogenic fungi Bipolaris species, which usually infect rice, maize and sorghum. The topics covered include the organisms that produce the various ophiobolins, the structural variations of ophiobolins, the biological actions of ophiobolins in plants, animals and microorganisms, and the mode of action and the possible use of ophiobolin A as a calmodulin antagonist.