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Biomedical subjects

G Corradin

Publications and source records attributed to G Corradin.

159 records · Page 9Linked to original sources
PubMed1981

Lymphocyte specificity to protein antigens. III. Capacity of low responder mice to beef cytochrome c to respond to a peptide fragment of the molecule.

Lymph node cells derived from A.TH or A.TL mice primed with beef cytochrome c show striking patterns of reactivity when assayed in vitro for antigen-induced T cell proliferation. Whereas cells from A.TH mice respond specifically to beef cytochrome c or peptides composed of amino acids 1-65 and 81-104, cells from A.TL mice respond neither to beef cytochrome c nor to peptide 1-65, but proliferate following exposure to either peptide 81-104 or to a cytochrome c hybrid molecule in which the N-terminal peptide of beef (1-65) was substituted by a similar peptide obtained from rabbit cytochrome c. Thus, T cells from mice phenotypically unresponsive to beef cytochrome may, in fact, contain populations of lymphocytes capable of responding to a unique peptide, the response to which is totally inhibited when the same fragment is presented in the sequence of the intact protein.

Animals↗
PubMed1981

Clonal analysis of the BALB/c T cell proliferative response to apo beef cytochrome c.

Murine T cell clones that proliferated specifically in response to the protein antigen apo cytochrome c were derived and maintained in continuous culture. Two distinct clonotypes were observed with respect to the proliferative responses observed when a variety of peptides prepared from several species of cytochrome c were tested. These 2 clonotypes appeared to recognize 2 different regions in the cytochrome c molecule. Only 1 of the 2 clonotypes tested demonstrated helper cell activity for antibody formation in vitro.

Animals↗
PubMed1979

Lymphocyte specificity to protein antigens. II. Fine specificity of T-cell activation with cytochrome c and derived peptides as antigenic probes.

Murine T-lymphocyte specificity was determined in a system of antigen driven in vitro T-cell proliferation using cytochrome c molecules from different species, their derived peptides and reconstituted hybrid proteins. It was observed that primed T cells could discriminate between peptide fragments which differed from each other at a single amino acid residue. These conclusions were substantiated by the pattern of cross-reactivity noted in the response of closely related cytochrome c proteins as well as when artificial hybrid molecules reconstituted by the covalent linkage of peptide fragments were analyzed. The pattern of specificity observed appeared to be haplotype (BDF1) dependent although similar conclusions about the fine specificity of T cells in the response to cytochrome c have been obtained in other strains but associated with different residues.

Amino Acid Sequence↗
PubMed1977

Lymphocyte specificity to protein antigens. I. Characterization of the antigen-induced in vitro T cell-dependent proliferative response with lymph node cells from primed mice.

An in vitro assay which measures antigen-induced proliferation of primed murine lymph node cells is described. The response is mediated by T eclls since it can be obtained by using nylon wool-passed lymphocytes (less than 1% Ig+ cells) and it can be abolished by treatment with anti-Thy 1.2 and C. Furthermore, LN cells from nu/nu mice injected with antigen do not demonstrate antigen-induced proliferation in contrast to the response observed in euthymic littermate controls. Other relevant parameters of this proliferative assay include the observations that the response is highly antigen specific, can be seen as early as 4 days and as late as 60 days after in vivo priming, is restricted to the use of certain sets of LN when animals are injected subcutaneously at the base of the tail, and can be seen with LN cells from mice primed with antigen in either CFA or ICFA. The ease of the assay coupled with its specificity and quantitative dimensions provides a direct and simple method to evaluate processes involved in antigen-induced murine T lymphocyte activation.

Animals↗
PubMed1971

Reconstitution of horse heart cytochrome c: interaction of the components obtained upon cleavage of the peptide bond following methionine residue 65.

Horse heart cytochrome c can be divided into a heme peptide of 65 residues (H65CNBr) and a nonheme peptide of 39 residues (N39CNBr) by treatment of the molecule with cyanogen bromide. Upon mixture of the two peptides in aqueous solution, a 1: 1 complex with properties closely resembling those of the parent heme protein can be formed. The reaction can conveniently be effected in sodium acetate buffer of pH 4.7, with the H65CNBr in the reduced form. The heme peptide is predominantly in the high-spin state under these conditions, and, upon the addition of N39CNBr, is converted to a complex with absorption and circular dichroism spectra which correspond closely to those of ferrocytochrome c. If N39CNBr is added to the oxidized form of H65CNBr, the spectral properties of the product differ appreciably from those of the parent protein. A complex with absorption and circular dichroism spectra comparable to those of ferricytochrome c can readily be obtained, however, through oxidation of the product of the reaction of N39CNBr with H65CNBr in the reduced state. The complex formed in this manner has an absorption band at 695 nm, exhibits no tryptophan or tyrosine fluorescence, and is active in the succinate oxidase system.

Animals↗
PubMedDate not supplied

Antigen degradation by macrophages as an obligatory step in the presentation of antigen to T lymphocytes.

Evidence is presented which supports the hypothesis of protein degradation taking place in macrophages as a part of the presentation of antigen to T lymphocytes. It is postulated that the ability of T cells to recognize both native and denatured forms of the same protein is dependent upon degradation of both forms of the protein to yield the same peptides and thus results in the stimulation of identical subsets of T cells. The occasional observation of a lack of cross-reactivity could result if the native antigen is particularly resistant to the denaturing conditions found within macrophages.

Antibody Formation↗
PubMedDate not supplied

Induction of a cytotoxic T lymphocyte response by immunization with a malaria specific CTL peptide entrapped in biodegradable polymer microspheres.

We have previously reported that biodegradable polymer microspheres (MS) are capable of eliciting strong and long-lasting antibody and T cell proliferative responses for either natural protein antigens or synthetic peptides. In this study, we investigated the possibility of inducing antigen-specific cytotoxic T lymphocyte (CTL) responses in vivo with a short synthetic peptide from the circumsporozoite (CS) protein of Plasmodium berghei (Pb) 252-260 by using different MS formulations. We show that injection of mice with a short CTL epitope microencapsulated in MS or adsorbed on empty MS enhanced a specific CTL response comparable to that obtained with the incomplete Freund's adjuvant (IFA) formulation, indicating that MS are a potent antigen delivery system/immunostimulant for CTL response. These results might be of practical interest for MS preparation and development of subunit vaccines.

Animals↗
PubMedDate not supplied

Immunogenicity of Plasmodium falciparum circumsporozoite protein multiple antigen peptide vaccine formulated with different adjuvants.

Only low antibody levels were obtained from vaccinating human volunteers with single-chain peptide from the Plasmodium falciparum circumsporozoite protein (PfCSP). This resulted in modest protection against sporozoite challenge. In addition, HLA restriction limits the probability of synthesis of a vaccine effective for a diverse population. We report immunization studies with a multiple antigen peptide (MAP) system consisting of multiple copies of a B-cell epitope from the central repeat region of the PfCSP in combination with a universal T-cell epitope, the P2P30 portion of tetanus toxin. This MAP4(NANP)6P2P30 vaccine was highly immunogenic in four different strains of mice when used with various safe and nontoxic adjuvants. When this MAP vaccine was encapsulated in liposomes with lipid A and adsorbed to aluminium hydroxide and given three times at 4-week intervals, the resultant antibody prevented 100% of sporozoites from invading and developing into liver stage infection. This high degree of immunogenicity of MAP4(NANP)6P2P30 vaccine formulated in liposomes, lipid A and aluminum hydroxide provides the foundation for consideration of human trials with this formulation.

Adjuvants, Immunologic↗
PubMedDate not supplied

Inhibition of antigen-induced T-cell clone proliferation by antigen-specific antibodies.

Attempts to inhibit the recognition of soluble antigens by T lymphocytes using antibodies specific for the antigen in question have been uniformally unsuccessful, in contrast to the observed specific inhibition of antibody generation by B cells. One exception is the unique situation whereby anti-hapten antisera inhibit the T-cell proliferative responses observed when hapten-specific T lymphocytes or clones are cultured with hapten-derivatized cells or proteins. The inability to inhibit T-cell functions by antigen-specific antibodies has been interpreted in several ways: (1) T cells possess a different repertoire from B cells; (2) the antibodies tested recognize epitopes present on the native antigen, whereas T cells recognize non-native (processed) structures; (3) the antigenic determinant(s) recognized by T cells on the surface of antigen presenting cells are either not accessible to antibodies, or are present in low amounts. The development of antigen-specific T-cell clones and monoclonal antibodies both specific for the same antigenic determinants now allows this question to be investigated definitively. Here, we report for the first time the specific inhibition of antigen-induced T-cell clone proliferation by a monoclonal antibody directed against the relevant soluble protein antigen.

Animals↗
PubMedDate not supplied

H-2-restricted cytolytic T cells specific for HLA can recognize a synthetic HLA peptide.

It is generally accepted that T lymphocytes recognize antigens in the context of molecules encoded by genes in the major histocompatibility complex (MHC). MHC class II-restricted T cells usually recognize degraded or denatured rather than native forms of antigen on the surface of class II-bearing antigen presenting cells. It has recently been shown that short synthetic peptides corresponding to mapped antigenic sites of the influenza nucleoprotein (NP) can render uninfected target cells susceptible to lysis by NP-specific class I-restricted cytolytic T cells (CTL). These and earlier experiments that showed specific recognition of NP deletion mutant transfectants suggest that class I-restricted recognition might also involve processed antigenic fragments. One important issue arising from these studies is whether the model applies not only to viral proteins that are expressed internally (such as NP) but also to antigens normally expressed as integral membrane proteins at the cell surface. We have recently isolated class I-restricted mouse CTL clones that recognize class I gene products of the human MHC (HLA) as antigens in mouse cell HLA-transfectants. Here we show that these anti-HLA CTL can lyse HLA-negative syngeneic mouse cells in the presence of a synthetic HLA peptide. These results suggest that the model applies generally.

Animals↗
PubMedDate not supplied

Natural antibody response to Plasmodium falciparum Exp-1, MSP-3 and GLURP long synthetic peptides and association with protection.

A longitudinal study was undertaken in Burkina Faso among 293 children aged 6 months to 9 years in order to determine the correlation between an antibody response to several individual malarial antigens and malarial infection. It was found that the presence of a positive antibody response at the beginning of the rainy season to three long synthetic peptides corresponding to Plasmodium falciparum Exp-1 101-162, MSP-3 154-249 and GLURP 801-920 but not to CSP 274-375 correlated with a statistically significant decrease in malarial infection during the ongoing transmission season. The simultaneous presence of an antibody response to more than one antigen is indicative of a lower frequency of malarial infection. This gives scientific credibility to the notion that a successful malaria vaccine should contain multiple antigens.

Animals↗