Biomembranes最新文献

The transplantation antigens are the phenotypic products of genes which control histocompatibility in vertebrate species. The products of major histocompatibility locus of the mouse, H-2, have been studied as a model. The H-2 transplantation antigens are expressed on cellular membranes in all tissues examined. These gene products have been isolated from cells associated with subcellular membranes. These membranes have been assayed both for their antigen content (antigenicity) and for their capacities to induce a primary humoral and a cell-mediated response (immunogenicity). In all tissues examined, the H-2 antigens (products of the K and D regions of H-2) were found expressed in high concentration on cell surface membrane. However, immunogenic activity was observed only with spleen and thymus preparations, consisting mainly of intracellular membranes (MLP). Immunogenic MLP was also isolated from lymphoblast and fibroblast cells, and again was derived mainly from endoplasmic reticulum. In other tissues, such as liver, kidney, and erythrocytes, H-2 antigens were found only on surface membrane and in an antigenic but nonimmunogenic form. A novel method for tagging surface membrane of mammalian cells is presented. It consists of binding, to whole cells in a covalent linkage, purified preparations of the beta-galactosidase of E. coli. The bound enzyme has proved to be an unambiguous marker for surface membrane. With this marker, the stability of surface membrane to shear forces during homogenization could be assessed. A number of considerations suggest that immunogenicity of transplantation antigens may be due to factor(s) present on the membranes in addition to the H-2 antigenic determinants. There are indications that these factors may be controlled by the I region of the H-2 complex. It is interesting to note that normal tissues which have Ia antigens on their surface membranes yield immunogenic MLP (spleen and thymus), whereas those without Ia surface antigens yield an antigenic MLP that has no immunogenic capacity (liver, kidney, and erythrocytes).

Significant advances have been made over the past few years in elucidating the genetics, the chemical composition, and, more recently, the in situ relation of the major histocompatibility antigens of the mouse and man. Attempts to map the arrangement of individual antigens on the surface of cells have revealed that some antigens specified by a given subregion of both the H-2 and HL-A systems are in close proximity on the cell membrane and that attachment of antibody to one site to a certain degree blocks or inhibits the binding of antibody to the adjacent site. Allelic antigens in the H-2 system tend to inhibit binding. H-2D and H-2K antigens show either inhibition or noninteraction, possibly reflecting a cis-trans effect. Unlike with the H-2, inhibition of binding occurs only between HL-A antigens specified by homologous chromosomes. Also, a number of instances have been noted where inhibition of binding is unidirectional, possibly reflecting a polymeric nature of antigen or stratification of moieties at cell surface. Inhibition of antibody attachment between several alloantigenic systems on thymocytes in mice and also a variation in the mobility of the histocompatibility antigens suggest that the moieties bearing histocompatibility antigens are comprised of several gene products. Further work is needed to establish the validity of this assumption and to fully define the composition of these units. Ample data have been obtained from both biological and biophysical experiments to support the suggestion that single or multiple complexes of glycoproteins can move in the plane of the membrane. Although the composition of these cell membrane components remains a question, direct visualization by fluorescence and electron microscopy indicates that these moieties are small and, under natural conditions, distributed uniformly over the cell surface. Direct and indirect labeling techniques have shown that the complexes have no fixed position in the cell membrane and can be displaced laterally in the plane of the membrane without affecting the distribution of other surface molecules, such as sIg and species-specific antigens. Additional evidence suggests that H-2D and H-2K antigen complexes, as well as their gene products specified by different parent chromosomes, may be displaced separately. These observations are especially interesting and must be reconciled and data obtained by proximity analysis which indicate an association of some allelic products and possibly certain combinations of D and K antigens. Whether the differences noted in reactivity of the various surface antigens following attachment of antibodies are attributable to difference in size or to differences in the manner of their intercalation in the cell membrane remains to be elucidated. The rapid advances in elucidation of the molecular structure of biological membranes suggest that experimental work should be done on the biophysics of the structure of the antigenic sites and the me