PubMed Health⌕ Search

Biomedical subjects

D E Parks

Publications and source records attributed to D E Parks.

At least 19 recordsLinked to original sources
PubMed1992

Immunogenic peptides corresponding to the dominant antigenic region alanine-597 to cysteine-619 in the transmembrane protein of simian immunodeficiency virus have a propensity to fold in aqueous solution.

Two synthetic peptides corresponding to the N- and C-terminal halves of a 23 amino acid sequence representing an immunodominant domain of the simian immunodeficiency virus of macaque origin (SIVmac) were examined for conformational preferences in aqueous solution by proton nuclear magnetic resonance methods. The two constituent peptides, termed A12-7 (Ala597-Ile-Glu-Lys-Tyr-Leu-Glu-Asp-Gln-Ala-Gln607) and A12-9 (Leu608-Asn-Ala-Trp-Gly-Cys-Ala-Phe-Arg-Gln-Val-Ser619), were found to contain a considerable conformational preference for states in which the backbone phi and psi angles populate the alpha region of the Ramachandran plot. Further, for peptide A12-9, the types and intensities of the nuclear Overhauser effect (NOE) connectivities between protons in the polypeptide backbone suggest that these states appear to include helical turns. The temperature dependence of the amide proton chemical shifts indicates that some degree of intramolecular hydrogen bonding occurs in these peptides. These results are consistent with a model in which immunogenic peptides which induce antibodies reactive with the intact protein from which the peptide sequence was derived contain conformational preferences in water solution for states other than the extended-chain forms typically found in "random coil" peptides.

Alanine↗
PubMed1991

Lack of evidence for HIV-2 infection among at-risk individuals in Brazil.

Recent reports have indicated the possibility that HIV-2 has been introduced into groups at risk for AIDS in Brazil. We studied sera collected in 1987 and 1988 from 1,821 at-risk individuals from diverse regions in Brazil. Of the 1,821 sera, 367 (20%) were confirmed as being positive for HIV-1 antibodies by enzyme-linked immunosorbent assay (ELISA), immunofluorescence (IF), and Western blot. An additional 33 (2%) sera displayed some reactivity to HIV-2-infected cells by IF. All 33 sera were subsequently tested in HIV-1 and HIV-2 Western blots as well as an ELISA using HIV-1- or HIV-2-specific peptides. All sera were confirmed as positive for HIV-1 and negative for HIV-2 antibodies in both assays. We conclude that caution should be used in the interpretation of serologic cross-reactivity between HIV-1 and HIV-2 and that there is no evidence that HIV-2 has entered groups at risk for HIV infection in Brazil.

Blotting, Western↗
PubMed1989

Immunochemistry of the dominating antigenic region Ala582 to Cys604 in the transmembranous protein of simian and human immunodeficiency virus.

The immunochemistry of two homologous uniquely antigenic peptides representing Ala582 to Cys604 in the transmembrane proteins of simian immunodeficiency virus of rhesus macaque origin, SIVmac (closely related to HIV-2) and HIV-1 (strain HTLV-IIIB) was characterized at the resolution of single amino acids. Five different antigenic sites were identified in the SIVmac peptide by use of 34 mAb against this peptide and two different sites were similarly demonstrated in the HIV-1 peptide by use of 10 peptide-specific mAb. Within some sites the mAb could be subgrouped to show a progressively more narrow epitopic dependence on amino acids in the central part of the site. Three SIVmac peptide mAbs had a remarkably narrow amino acid dependence, Glu584 and Tyr586. Anti-peptide mAbs reacting with the site Trp596 to Gln602 effectively blocked the capacity of the peptide to react with human postinfection HIV-2 antibodies previously demonstrated to have a restricted reactivity involving this site. No similar blocking was seen when mAb specific for Leu587 to Gln590 were used except with a single broadly reacting HIV-2 serum, which depended on an amino acid at a distance of only 6 residues, Trp596. A cross-reacting site involving amino acids Ala582 to Glu588/Lys588 was identified with mAb and rabbit hyperimmune sera against the two peptides. This site was not accessible in the intact transmembrane proteins as determined by ELISA and Western blot tests. Antipeptide mAb against other sites as well as rabbit sera reacted strongly in these tests and can be used as type-specific, component-unique reagents.

Alanine↗
PubMed1989

The chemistry of site-directed serology for HIV infections.

The advent of site-directed serology has provided a specific and simplified means of distinguishing antibody responses to the two types of human immunodeficiency virus (HIV) in an outbred population. Remarkably, human sera containing HIV antibodies and simian sera containing simian immunodeficiency virus (SIV) antibodies had a very narrow amino acid dependence in the 23 residue long peptide, 582Ala-604Cys, used as antigen. A single dominating antigenic site was demonstrated in the C-terminal part of the peptide--596Trp-602Gln for HIV-2 and SIV antibodies and 597Gly-602Leu for HIV-1. A minor fraction of HIV-1 antibodies also reacted with a second site, 588Lys and 589Asp. These data define the precise amino acid dependence of a uniquely immunogenic site in the folded transmembrane protein of HIV and facilitate the optimizing of peptide antigens for site-directed serology.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Correlation of fetal kidney and testis congenic graft survival with reduced major histocompatibility complex burden.

Prolonged survival was enjoyed by fetal and postnatal testis and midgestational renal grafts transplanted beneath the renal capsule of adult congenic mice, confirming previous findings in nonimmunosuppressed outbred rats (3,5). The strategies that enable immature tissues to escape rejection in a graft survival assay were studied by comparing expression of major histocompatibility class I and class II protein and messenger ribonucleic acid (mRNA) in each tissue at different ages. In general, graft survival was best when class I and II expression was low. After transplantation, surviving kidney and testis grafts both showed marked induction of class I and II mRNA measured using donor and recipient-specific oligonucleotide probes. Immunohistochemically detected protein of both classes, however, could not be found in the kidney and was minimal in the testis. Fetal tissues appear to express lower levels of protein and mRNA--and, although invading lymphocytes may induce expression of class I and II mRNA after transplantation, protein was not inducible. The failure of these tissues to express significant levels of transplantation antigens may explain the prolonged survival of these immature grafts.

Animals↗
PubMed1988

Fetal and postnatal testis shows immunoprivilege as donor tissue.

We evaluated the immunogenicity of the testis by transplanting adult, postnatal, and fetal rat testicular tissue into outbred adult female and male rats for 10 days. Testis grafts were evaluated morphometrically and histologically, and selectively compared to renal grafts previously reported in part. Testis grafts from days 15 to 21 of gestation, and from three, nine, 12 and 15 days after birth showed an overall increase in growth, with maintenance of architecture and minimal lymphocytic infiltrate. In contrast, only fetal renal tissue from days 15 to 17 demonstrated an increase in growth with maintenance of architecture and minimal lymphocytic infiltrate; grafts from later in gestation grew only slightly and showed progressive deterioration in architecture with an increasing lymphocytic infiltrate. Fifteen day fetal testis grafts were also implanted for longer intervals up to 45 days. The fetal testis grafts implanted for 20 and 30 days showed an increase in size with maintenance of architecture and minimal lymphocytic infiltrate. The observed fetal and postnatal testis growth in the non-immunosuppressed adult host makes compelling further studies directed at determining those factors contributing to the decreased immunogenicity of this organ.

Age Factors↗
PubMed1988

Site-directed ELISA identifies a highly antigenic region of the simian immunodeficiency virus transmembrane glycoprotein.

The transmembrane glycoprotein (gp32) of the simian immunodeficiency virus (SIV) contains a highly antigenic region that includes amino acid residues 606-628. A synthetic peptide representing this region was highly immunoreactive with sera from SIV-infected primates in a site-directed enzyme-linked immunosorbent assay (ELISA). This reactivity extended across four primate species from three genera and identified infection with at least two distinct isolates of SIV. This site-directed ELISA represents a simple, accessible method with broad specificity for screening large numbers of primates for antibodies against SIV.

Amino Acid Sequence↗
PubMed1987

Modulation of the induction and circumvention of immunological tolerance to human gamma-globulin by interleukin 1.

As with agents capable of causing the release of IL 1, IL 1 itself is capable of modulating certain tolerance-inducing events. Under the condition used in the present study, it previously has been firmly established that injection of A/J mice with DHGG induces a state of antigen-specific tolerance in both T helper (Th) and B cells. The tolerance in the B cell is of long duration, whereas that in the B cell is of shorter duration. Recombinant IL 1 (rIL 1) given shortly after the tolerogen DHGG results in the inhibition of the induction of tolerance resulting in antibody production. The induction of tolerance is inhibited at both its antigen-specific Th cell and B cell levels, although the latter may be caused by the former. The inhibition of the induction of tolerance by rIL 1 is not correlated to the generation of antigen-specific T suppressor cells. IL 1 mimics lipopolysaccharide and 8-bromoguanosine, which generate IL 1 production, in its ability to interfere with the in vivo induction of tolerance. However, in contrast to these latter mitogens which cause both terminal differentiation of B cells and IL 1 production, IL 1 itself does not cause in vivo circumvention of long-term tolerant Th cells in the presence of competent B cells and antigen. These latter findings suggest that a signal(s) in addition to those delivered by IL 1 is required for activation of the B cell compartment recovering from tolerance to antibody production. AHGG (immunogen) is a potent generator of IL 1 release, whereas DHGG has no effect on IL 1 release from macrophages and AHGG inhibits the induction of tolerance by DHGG. These latter results suggest that the lack of an IL 1 signal may be responsible for the deliverance of a tolerogenic rather than an immunogenic signal to the Th cell.

Animals↗
PubMed1985

Enhancement of the in vivo antibody response by an 8-derivatized guanine nucleoside.

The capacity of the C8-substituted guanine ribonucleosides to enhance the in vivo humoral immune response to the protein antigen, human gamma globulin (HGG), in A/J mice was evaluated. It has been shown recently that the C8-substituted guanine ribonucleosides are a new class of potent adjuvant for humoral immune responses to the sheep erythrocyte antigen. The current studies extend these findings to HGG with 8-bromoguanosine (8BrGuo), a representative of this group of nucleosides. The adjuvant activity of 8BrGuo in this system is highly dose and time dependent. Although 8BrGuo enhanced responses when injected either early (Day 0) or late (Day 4 or 5) after immunization, its administration on Day 1 or 2 most often led to no enhancement, suggesting that 8BrGuo may act on two events separated by a resistant stage in an ongoing immune response. The plaque-forming cell (PFC) response to HGG was enhanced optimally at doses as low as 1 mg 8BrGuo/mouse administered either on the day of immunization or 4 days thereafter. In contrast, however, serum anti-HGG antibody concentration assayed by enzyme-linked immunosorbent assay (ELISA) was enhanced only at doses of 10 mg or more, injected on the day of immunization, but doses as low as 1 mg were effective on Day 4. 8BrGuo was also an effective adjuvant when injected after antigen administration in incomplete Freund's adjuvant or when administered by several different routes (intraperitoneal, subcutaneous, oral).

Adjuvants, Immunologic↗
PubMed1985

Tolerance induction in antigen-specific helper T cell clones and lines in vitro.

The induction of T cell tolerance in vitro was investigated by using HGG-specific murine helper T cell (Th) clones and cell lines. It was found that exposure of Th to monomeric HGG (tolerogen) for 18 hr rendered the Th unable to reconstitute the PFC response of HGG-primed B cells. The tolerant state was not a result of Th cell death, as up to 100% of Th could be recovered after exposure to the monomer, and in addition, the recovered cells proliferated in response to IL2. B cells were shown not to be significantly affected by the presence of monomeric HGG in amounts calculated to be carried over from the tolerization cultures into the assay cultures. Consequently, it was concluded that interaction between Th and monomeric HGG induced unresponsiveness at the T cell level. A comparison of the tolerogenic potential of monomeric, soluble, and aggregated HGG revealed that only the monomer could induce tolerance in Th. Monomeric HGG was also shown to induce tolerance in an antigen-specific manner. Th reactive to HGG could be tolerized by monomeric HGG, but not Th reactive to FGG or OVA. Helper function of Th was also shown to be antigen specific in that HGG-reactive Th helped only HGG-primed B cells. Certain HGG-specific Th clones were found to be refractory to tolerization with monomeric HGG, whereas other clones derived from the same uncloned cell line were tolerizable.

Animals↗
PubMed1985

Active transformation of tolerogenic to immunogenic signals in T and B cells by 8-bromoguanosine.

The injection of deaggregated human gamma-globulin (DHGG) into A/J mice results in the establishment of a state of unresponsiveness to subsequent challenge with immunogenic aggregated human gamma-globulin (AHGG). Administration of the B cell activator 8-bromoguanosine (8BrGuo) 3 hr after administration of DHGG converts the tolerogen to an immunogen and results in an antibody response of even greater magnitude than the primary response elicited by AHGG alone. Adoptive transfer studies with separated populations of T and B cells demonstrated that although transformation of the tolerogenic signal to an immunogenic signal involves effects of 8BrGuo on both T cells and B cells, the major effect appears to be activation of antigen-specific T cells that would otherwise become tolerant. Modulation of T cell tolerance could conceivably be mediated either by direct or indirect mechanisms. Interestingly, optimal responsiveness of B cells from animals treated with DHGG and 8BrGuo is not a T cell-independent event, but requires antigen-reactive T cells. 8BrGuo is not able to override unresponsiveness when given 10 to 20 days after tolerance induction, at a time point when both T and B lymphocytes are tolerant. However, when given at day 60, when T cells (but not B cells) remain tolerant to this antigen, the nucleoside is able to terminate the tolerant state prematurely, possibly by providing an alternate T helper-like signal directly to B cells or by recruiting nonspecific functional T helper cells.

Animals↗
PubMed1984

Long-term suppressor cell lines. I. Demonstration of suppressive function.

Suppressor T cell (Ts) lines have been generated and maintained in culture for over one year. Cells from these lines suppress proliferation by primed lymph node cells and antibody production by primed spleen cells. Ts were originally obtained from either spleens of mice rendered tolerant to human gamma globulin (HGG) or short-term cultures of normal spleen cells. Ts from these two sources have previously been shown to exhibit antigen specificity in that only HGG-specific immune responses were suppressed. Prolonged culture of Ts, however, leads to 2 events: an enrichment for suppressive activity in the cultures; and a polyclonal activation of Ts which is demonstrated by the acquired ability of Ts cell lines to regulate responses to antigens other than HGG. Ts cell lines still contain HGG-specific Ts which can be isolated by their capacity to bind to HGG-coated plates. Only HGG-specific immune responses are suppressed by the HGG-binding Ts.

Animals↗
PubMed1984

Long-term suppressor cell lines. II. Suppressor-target interactions.

Long-term nonhybridized murine suppressor T cell (Ts) lines, some of which have been in culture for over one year, are genetically restricted in their ability to suppress proliferation of primed lymph node cells (LNC). The genetic restriction maps to the I region of the major histocompatibility complex and resides in either the I-A, I-E or I-J locus. Suppressive activity is only slightly decreased following irradiation of the Ts with 2000 rds. The target for suppressive activity expressed by Ts cell lines is the helper T cell as suggested by experiments in which LNC proliferation was maximally suppressed when Ts were present early in the assay culture. The identity of the target cell was confirmed by experiments in which Ts were shown to suppress the anti-human gamma globulin plaque-forming cell response resulting from co-culture of primed B cells with cloned human gamma globulin-specific helper T cells.

Animals↗
PubMed1982

Deregulation of idiotype expression. Induction of tolerance in an anti-idiotypic response.

The induction of tolerance in an anti-idiotypic response was attempted by in vivo exposure to excess idiotype. Monoclonal immunoglobulin from the anti-p-azobenzenearsonate (ABA) hybridoma R16.7 was used as a representative of cross-reactive idiotype-positive (CRI+) antibodies because this hybridoma protein (HP) shares one or more closely related public idiotypic determinants with the serum CRI in A/J mice. Immunologic unresponsiveness was established by a single injection of the R16.7 idiotype and persisted for at least 6 wk. The level of circulating anti-idiotypic antibodies in tolerized A/J mice was significantly depressed after immunogenic challenge with eigher antigen, ABA-keyhole limpet hemocyanin (KLH), or the idiotype R16.7 HP. Experimental depletion of anti-idiotypic antibodies by tolerization allowed assessment of immunoregulation within this altered idiotype-anti-idiotype network. Deregulation of idiotype expression in tolerized mice challenged with ABA-KLH was manifest with up to 96% of the anti-ABA antibodies cross-reacting with the R16.7 idiotype. This selective enhancement of a major idiotype was accomplished without substantial alteration of the level of the overall anti-hapten response. Both the unresponsiveness established in anti-idiotypic antibody-producing cells and the enhanced synthesis in idiotype-producing cells were stable upon adoptive transfer into lethally irradiated, syngeneic recipients. Finally, previous immunization with the antigen ABA-KLH interfered with the induction of unresponsiveness to the idiotype. This interference is presumed to be mediated by prior activation of anti-idiotypic cells and/or antibody because injection of antigen with tolerogenic idiotype did not abrogate tolerance induction.

Animals↗