Antigenic correlation between rat brain synaptic vesicles and rat bone marrow B lymphocytes

Summary Rabbit anti-rat brain synaptic vesicle serum reacted with thymocytes and B lymphocytes in cytotoxicity and immunofluorescence assays. Quantitative absorption analysis revealed that this antiserum contained antibodies specific for antigenic determinants on the surface membrane of a subpopulation of rat bone marrow B lymphocytes.This work was supported by the Republic of Serbia Research Fund, Belgrade.     

The role of glycosylation in protein antigenic properties

Glycosylation of proteins is a common event and contributes to protein antigenic properties. Most data have been obtained from model studies on glycoprotens with well-defined structure or synthetic glycopeptides and their respective monoclonal antibodies. Antibodies raised against glycoprotein antigens may be specific for their carbohydrate units which are recognized irrespective of the protein carrier (carbohydrate epitopes), or in the context of the adjacent amino acid residues (glycopeptidic epitopes). Conformation or proper exposure of peptidic epitopes of glycoproteins is also frequently modulated by glycosylation due to intramolecular carbohydrate-protein interactions. The effects of glycosylation are broad: glycosylation may 'inactivate' the peptidic epitope or may be required for its reactivity with the antibody, depending on the structure of the antigenic site and antibody fine specificity. Evidence is increasing that similar effects of glycosylation pertain to T cell-dependent cellular immune responses. Glycosylated peptides can be bound and presented by MHC class I or II molecules and elicit glycopeptide-specific T cell clones. Received 5 July 2001; received after revision 9 October 2001; accepted 11 October 2001     

Stimulating determinants of the secondary mixed lymphocyte reaction (MLR-II)]

An anti-Ia immune serum (A . TL anti-A . TH) directed to the antigens of the stimulating cell, blocked the MLR-II. A significant correlation was observed between the anti-Ia reactivity of the immune serum, studied against a panel of eleven original H-2 haplotypes and the reactivity against the same panel of the in vitro primed responding cells (A . TL anti-A . TH). These results confirm the hypothesis that Ia antigens are the structures stimulating the MLR-II.     

Mode of action of a soluble restricted factor, a suppressor of the allogeneic proliferative response in man

Appearance of "suppressor cells" is induced by in vitro hyperimmunization of lymphocytes against allogeneic cells, incompatible for one HLA-DR antigen. These "suppressor cells under certain conditions, release in the culture medium, "suppressor factors" of the in vitro allogeneic proliferative response in Man. They are not immunoglobulins and act in a non specific way towards the stimulators. Only one of them is restricted to some individuals. This is shown when either responders or stimulators are incubated for different periods, with the "suppressor factors" prior to the primary mixed lymphocyte reaction (MLRI). The beneficial effect of transfusions on kidney graft survival, could be, in part, explained by a suppressor mechanism, analogous to the one described in vitro.     

Modification of mixed lymphocyte reactivity between DLA-identical dog sibs, after in vivo sensitization

Mixed lymphocyte reactions (MLR) with cells from DLA-identical dog sibs are nonresponsive either in primary or in secondary interactions after in vitro priming. However, lymphocytes from animals sensitized in vivo against DLA-identical sibs can show increased proliferative response to their immunizing donor. The kinetics of this reaction are similar to MLR across the DLA-barrier, although its intensity is less important. This proliferation may reflect minor histocompatibility antigenic differences.     

Long-term production and culture of clones of human T-lymphocytes

Culture of blood T lymphocytes collected from normal individuals and cancer patients were carried out in presence of T cell growth factor (TCGF); these cultures presented cytotoxic activity directed against different targets (lectin activated cells, autologous cancer cells, antibody coated cells and K 562). In order to study separately the different effector subpopulations, isolation of single cultured cells were performed with the help of a micropipette under microscope and monoclonal cultures were carried out in presence of TCGF. In the preliminary cytotoxic assays performed in the clones: (1) a marked activity directed against lectin targets was observed in many clones and (2) an important N K activity was exhibited by the clone 45 B9 (65% of the tested cells lysed human lymphoma K 562 cells).     

The value of good Biozzi antibody-producing strains of mice for the production of monoclonal antibodies]

We report here that using Biozzi's high and low responder strains of Mice in the preparation of monoclonal antibodies against human T lymphocytes, we observed with the high responder strain 1) a higher number of hybrids; 2) a huge increase in the proportion of hybrids secreting on antibody directed against human lymphocytes.     

Antigens of the blood group I and i on the surfacc of chicken erythrocytes]

I and i blood group antigens have been looked for an Chick erythrocytes using purified and 125 I anti-I, anti-i and anti-I i antibodies. No I antigen is found but i determinants are detected on embryo and adult Chick erythrocytes. This i reactivity is different from the embryonic and adult antigens respectively specific for embryo and adult Chick erythrocytes. Treatment of the erythrocytes with nuraminidase increases the i reactivity. Incubation with papain reduces the fixation of anti-i antibodies suggesting that the i determinant of Chick erythrocyte could be linked to glycopeptide chains.     

Mechanistic insights into the efficacy of cell penetrating peptide-based cancer vaccines

Immunotherapies are increasingly used to treat cancer, with some outstanding results. Immunotherapy modalities include therapeutic vaccination to eliminate cancer cells through the activation of patient’s immune system against tumor-derived antigens. Nevertheless, the full potential of therapeutic vaccination has yet to be demonstrated clinically because many early generation vaccines elicited low-level immune responses targeting only few tumor antigens. Cell penetrating peptides (CPPs) are highly promising tools to advance the field towards clinical success. CPPs efficiently penetrate cell membranes, even when linked to antigenic cargos, which can induce both CD8 and CD4 T-cell responses. Pre-clinical studies demonstrated that targeting multiple tumor antigens, even those considered to be poorly immunogenic, led to tumor regression. Therefore, CPP-based cancer vaccines represent a flexible and powerful means to extend therapeutic vaccination to many cancer indications. Here, we review recent findings in CPP development and discuss their use in next generation immunotherapies.     

Transfer of genetic information from T to B human lymphocytes during an immune response to herpes simplex virus]

Human blood lymphocytes carrying different allotypes were divided into B and T subpopulations and cultured in presence or in absence of ultraviolet inactivated Herpes Simplex Virus. Isolated B or T cells did not produce any antiherpetic activity. The B lymphocytes cultured in presence of 1 or 50% of the supernatant collected from virus exposed T cells synthesized on antiherpetic antibody with some allotypic markers of the T cell donor.     

What's new in the field of cancer vaccines?

The observation that in some cases tumors undergo spontaneous regression concomitantly with autoimmune manifestations has been interpreted as an indication of the involvement of the immune system in tumor rejection. This raised the conceptual possibility that the immune system could be used against the tumor. However, since tumor cells are poorly immunogenic by themselves, early attempts to develop immune-based approaches for cancer therapy saw the use of tumor cells transduced with genes coding for cytokines or costimulatory molecules to enhance in vivo immunity. The identification of cytotoxic T lymphocyte (CTL)-defined tumor associated antigens has allowed the development of new strategies for cancer immunotherapy. Novel adjuvants have been identified, and different modes of antigen delivery were devised which aim at inducing efficient CTL responses in patients. This review will discuss some of what is currently considered as relevant aspects of antitumor immunization.Received 19 July 2002; received after revision 11 December 2002; accepted 13 December 2002     

Antibody-dependent adherence of peritoneal cells of the rat to Trichinella spiralis larvae]

Washed peritoneal exudate cells from normal Rats firmly adhere to Trichinella spiralis larvae in the presence of serum containing anti-Trichinella antibodies. This effect is observed when muscle larvae, cells and dilutions of anti-sera are incubated for 1 hr. at 37 degrees C. No adherence takes place at 4 degrees C. Whole serum or its gammaglobulin fraction are active and effect is inhibited by the addition of Trichinella antigens. Complement is not essential since antiserum heated for 2 hrs. at 56 degrees C is active. Washed cells from infested animals do not adhere to the larvae in the absence of antiserum.     

Protective effect of interferon on the target cells of cytotoxic lymphocytes

Interferon treatment of sensitized T lymphocytes enhances cytotoxicity against target cells. On the contrary, the same treatment of the target cells alone protects them, whatever the cytotoxicity of effector cells might be. We suggest that the cells having once survived contact with cytotoxic T lymphocytes could become resistant to any new attack by the same cells.     

Gamma delta T cell receptors

Gamma delta (γ δ) T cells are among the least understood components of the immune system. While these cells appear to contribute uniquely to host immune competence, defining their functions in the context of host biology and pathology has been difficult. This is largely because it is unclear what antigens the γ δ T cell receptor repertoire is directed against. During the past year, there have been noteworthy advances in this area. Their significance in the context of γ δ T cell biology is discussed. Received 19 January 2006; received after revision 16 March 2006; accepted 26 May 2006     

Modification of lymphocyte response to phytomitogens by polycations and polyanions

Summary The stimulation effect on mitogen-induced lymphocyte response by polycationic compounds such as polylysine, DEAE dextran protamine and methylated albumin, is studied at different serum-protein concentrations and mitogen concentrations. It is suggested that the polar interaction between polycationic compounds and glycoproteins are of major importance for reactivity of lymphocytes to mitogens.     

T cell receptor bias for MHC: co-evolution or co-receptors?

In contrast to antibodies, which recognize antigens in native form, αβ T cell receptors (TCRs) only recognize antigens as peptide fragments bound to MHC molecules, a feature known as MHC restriction. The mechanism by which MHC restriction is imposed on the TCR repertoire is an unsolved problem that has generated considerable debate. Two principal models have been advanced to explain TCR bias for MHC. According to the germline model, MHC restriction is intrinsic to TCR structure because TCR and MHC molecules have co-evolved to conserve germline-encoded TCR sequences with the ability to bind MHC, while eliminating TCR sequences lacking MHC reactivity. According to the selection model, MHC restriction is not intrinsic to TCR structure, but is imposed by the CD4 and CD8 co-receptors that promote signaling by delivering the Src tyrosine kinase Lck to TCR–MHC complexes through co-receptor binding to MHC during positive selection. Here, we review the evidence for and against each model and conclude that both contribute to determining TCR specificity, although their relative contributions remain to be defined. Thus, TCR bias for MHC reflects not only germline-encoded TCR–MHC interactions but also the requirement to form a ternary complex with the CD4 or CD8 co-receptor that is geometrically competent to deliver a maturation signal to double-positive thymocytes during T cell selection.     

Polyisoprenyl glycolipids as targets of CD1-mediated T cell responses

T cells are well known to recognize peptide antigens presented by major histocompatibility (MHC) class I or class II molecules. More recently, the CD1 family of antigen-presenting molecules has been shown to present both mammalian and microbial glycolipid antigens for specific recognition by T cells. Human CD1c proteins mediate T cell recognition of polyisoprenyl glycolipids, evolutionarily conserved phosphoglycolipids, which function in glycan synthesis pathways. This family of antigenic molecules is particularly attractive for the study of the molecular features that control T cell recognition of self and foreign glycolipids because natural polyisoprenols from mammals, fungi, protozoa, mycobacteria and eubacteria differ in structure. Moreover, these naturally occurring structural differences can influence their recognition by CD1c-restricted T cells. This review of the structural diversity and evolutionary relationships of polyisoprenoid glycolipids emphasizes those features of polyisoprenyl glycolipid biosynthesis that are relevant to their functions as targets of CD1-mediated T cell responses. Received 16 March 2001; received after revision 19 April 2001; accepted 23 April 2001     

The role of adapter proteins in T cell activation

Engagement of antigen receptors on lymphocytes leads to a myriad of complex signal transduction cascades. Recently, work from several laboratories has led to the identification and characterization of novel adapter molecules, proteins with no intrinsic enzymatic activity but which integrate signal transduction pathways by mediating protein-protein interactions. Interestingly, it appears that many of these adapter proteins play as critical a role as the effector enzymes themselves in both lymphocyte development and activation. This review describes some of the biochemical and molecular features of several of these newly identified hematopoietic cell-specific adapter molecules highlighting their importance in regulating (both positively and negatively) signal transduction mediated by the T cell antigen receptor.