Faculty Opinions recommendation of Expression of major surface protein 2 variants with conserved T-cell epitopes in Anaplasma centrale vaccinates.

2002 ◽  
Author(s):  
Vishvanath Nene
Keyword(s):  
T Cell ◽  
Surface Protein ◽  
T Cell Epitopes ◽  
Major Surface Protein ◽  
Major Surface ◽  
Anaplasma Centrale

scholarly journals Expression of Major Surface Protein 2 Variants with Conserved T-Cell Epitopes in Anaplasma centrale Vaccinates

2002 ◽  
Vol 70 (2) ◽  
pp. 642-648 ◽  
Author(s):  
Varda Shkap ◽  
Thea Molad ◽  
Kelly A. Brayton ◽  
Wendy C. Brown ◽  
Guy H. Palmer
Keyword(s):  
T Cell ◽  
Vaccine Strain ◽  
Genomic Structure ◽  
Surface Protein ◽  
Amino Acid Sequences ◽  
T Cell Epitopes ◽  
Major Surface Protein ◽  
Genomic Arrangement ◽  
Major Surface ◽  
Anaplasma Centrale

ABSTRACT Major surface protein 2 (MSP-2), identified as a protection-inducing immunogen against Anaplasma marginale challenge, is an immunodominant outer membrane protein with orthologues in all examined Anaplasma species. Although immunization with live Anaplasma centrale has long been used to induce protection against acute disease upon challenge with virulent A. marginale, its MSP-2 structure and whether MSP-2 variants are generated during persistence of the vaccine strain was unknown. In this study, we showed that the A. centrale vaccine strain persisted for a minimum of 4 years postvaccination and generated sequential MSP-2 variants. Comparison of amino acid sequences encoded by A. centrale msp-2 transcripts from the initial postimmunization period and from sequential time points during persistence of the vaccine strain revealed a central hypervariable domain flanked by conserved amino and carboxy-terminal regions. This structure corresponded to that shown in A. marginale MSP-2, where the central hypervariable region encodes variant B-cell epitopes in the extracellular domain and the flanking transmembrane domains are rich in CD4+-T-cell epitopes. Importantly, at least four CD4+-T-cell epitopes are conserved between the two species, a finding consistent with A. marginale challenge triggering a recall response of CD4+ T cells induced by A. centrale vaccination. The genomic arrangement is conserved between A. centrale and A. marginale with multiple msp-2 pseudogenes and a single operon-linked expression site for the full-length msp-2. This conservation of both genomic structure for generating MSP-2 variants and the CD4+-T-cell epitopes between these two genetically distinct Anaplasma species indicates that they present a similar repertoire of MSP-2 epitopes to the immune system and that this similarity may be responsible for all or part of the A. centrale vaccine efficacy.

scholarly journals Anaplasma marginale Major Surface Protein 2 CD4+-T-Cell Epitopes Are Evenly Distributed in Conserved and Hypervariable Regions (HVR), Whereas Linear B-Cell Epitopes Are Predominantly Located in the HVR

2004 ◽  
Vol 72 (12) ◽  
pp. 7360-7366 ◽  
Author(s):  
Jeffrey R. Abbott ◽  
Guy H. Palmer ◽  
Chris J. Howard ◽  
Jayne C. Hope ◽  
Wendy C. Brown
Keyword(s):  
T Cell ◽  
B Cell ◽  
Surface Protein ◽  
Anaplasma Marginale ◽  
T Cell Epitopes ◽  
B Cell Epitopes ◽  
Major Surface Protein ◽  
Hypervariable Regions ◽  
Major Surface ◽  
Linear B

ABSTRACT Organisms in the genus Anaplasma express an immunodominant major surface protein 2 (MSP2), composed of a central hypervariable region (HVR) flanked by highly conserved regions. Throughout Anaplasma marginale infection, recombination results in the sequential appearance of novel MSP2 variants and subsequent control of rickettsemia by the immune response, leading to persistent infection. To determine whether immune evasion and selection for variant organisms is associated with a predominant response against HVR epitopes, T-cell and linear B-cell epitopes were localized by measuring peripheral blood gamma interferon-secreting cells, proliferation, and antibody binding to 27 overlapping peptides spanning MSP2 in 16 cattle. Similar numbers of MSP2-specific CD4+ T-cell epitopes eliciting responses of similar magnitude were found in conserved and hypervariable regions. T-cell epitope clusters recognized by the majority of animals were identified in the HVR (amino acids [aa] 171 to 229) and conserved regions (aa 101 to 170 and 272 to 361). In contrast, linear B-cell epitopes were concentrated in the HVR, residing within hydrophilic sequences. The pattern of recognition of epitope clusters by T cells and of HVR epitopes by B cells is consistent with the influence of protein structure on epitope recognition.

scholarly journals Major Histocompatibility Complex Class II DR-Restricted Memory CD4+ T Lymphocytes Recognize Conserved Immunodominant Epitopes of Anaplasma marginale Major Surface Protein 1a

2002 ◽  
Vol 70 (10) ◽  
pp. 5521-5532 ◽  
Author(s):  
Wendy C. Brown ◽  
Travis C. McGuire ◽  
Waithaka Mwangi ◽  
Kimberly A. Kegerreis ◽  
Henriette Macmillan ◽  
...  
Keyword(s):  
T Cells ◽  
Major Histocompatibility Complex ◽  
T Cell ◽  
Protective Immunity ◽  
Surface Protein ◽  
T Cell Epitopes ◽  
Major Surface Protein ◽  
Histocompatibility Complex ◽  
Cell Clones ◽  
Major Surface

ABSTRACT Native major surface protein 1 (MSP1) of Anaplasma marginale, composed of covalently associated MSP1a and MSP1b proteins, stimulates protective immunity in cattle against homologous and heterologous strain challenge. Protective immunity against pathogens in the family Anaplasmataceae involves both CD4+ T cells and neutralizing immunoglobulin G. Thus, an effective vaccine should contain both CD4+ T- and B-lymphocyte epitopes that will elicit strong memory responses upon infection with homologous and heterologous strains. Previous studies demonstrated that the predominant CD4+ T-cell response in MSP1 vaccinates is directed against the MSP1a subunit. The present study was designed to identify conserved CD4+ T-cell epitopes in MSP1a presented by a broadly represented subset of major histocompatibility complex (MHC) class II molecules that would be suitable for inclusion in a recombinant vaccine. Transmembrane protein prediction analysis of MSP1a from the Virginia strain revealed a large hydrophilic domain (HD), extending from amino acids (aa) 1 to 366, and a hydrophobic region extending from aa 367 to 593. The N terminus (aa 1 to 67) includes one 28-aa form A repeat and one 29-aa form B repeat, which each contain an antibody neutralization-sensitive epitope [Q(E)ASTSS]. In MSP1 vaccinates, recombinant MSP1a HD (aa 1 to 366) stimulated recall proliferative responses that were comparable to those against whole MSP1a excluding the repeat region (aa 68 to 593). Peptide mapping determined a minimum of five conserved epitopes in aa 151 to 359 that stimulated CD4+ T cells from cattle expressing DR-DQ haplotypes common in Holstein-Friesian breeds. Peptides representing three epitopes (aa 231 to 266, aa 270 to 279, and aa 290 to 319) were stimulatory for CD4+ T-cell clones and restricted by DR. A DQ-restricted CD4+ T-cell epitope, present in the N-terminal form B repeat (VSSQSDQASTSSQLG), was also mapped using T-cell clones from one vaccinate. Although form B repeat-specific T cells did not recognize the form A repeat peptide (VSSQS_EASTSSQLG), induction of T-cell anergy by this peptide was ruled out. The presence of multiple CD4+ T-cell epitopes in the MSP1a HD, in addition to the neutralization-sensitive epitope, supports the testing of this immunogen for induction of protective immunity against A. marginale challenge.

scholarly journals Physical Linkage of Naturally Complexed Bacterial Outer Membrane Proteins Enhances Immunogenicity

2007 ◽  
Vol 76 (3) ◽  
pp. 1223-1229 ◽  
Author(s):  
Henriette Macmillan ◽  
Junzo Norimine ◽  
Kelly A. Brayton ◽  
Guy H. Palmer ◽  
Wendy C. Brown
Keyword(s):  
T Cell ◽  
Membrane Proteins ◽  
Outer Membrane ◽  
Outer Membrane Proteins ◽  
Surface Protein ◽  
Host Cells ◽  
Effective Vaccine ◽  
T Cell Epitopes ◽  
Carrier Effect ◽  
Major Surface

ABSTRACTThe outer membrane proteins (OMPs) of bacterial pathogens are essential for their growth and survival and especially for attachment and invasion of host cells. Since the outer membrane is the interface between the bacterium and the host cell, outer membranes and individual OMPs are targeted for development of vaccines against many bacterial diseases. Whole outer membrane fractions often protect against disease, and this protection cannot be fully reproduced by using individual OMPs. Exactly how the interactions among individual OMPs influence immunity is not well understood. We hypothesized that one OMP rich in T-cell epitopes can act as a carrier for an associated OMP which is poor in T-cell epitopes to generate T-dependent antibody responses, similar to the hapten-carrier effect. Major surface protein 1a (MSP1a) and MSP1b1 occur as naturally complexed OMPs in theAnaplasma marginaleouter membrane. Previous studies demonstrated that immunization with the native MSP1 heteromer induced strong immunoglobulin G (IgG) responses to both proteins, but only MSP1a stimulated strong CD4+T-cell responses. Therefore, to test our hypothesis, constructs of CD4+T-cell epitopes from MSP1a linked to MSP1b1 were compared with individually administered MSP1a and MSP1b1 for induction of MSP1b-specific IgG. By linking the T-cell epitopes from MSP1a to MSP1b1, significantly higher IgG titers against MSP1b1 were induced. Understanding how the naturally occurring intermolecular interactions between OMPs influence the immune response may lead to more effective vaccine design.

Identification of Anaplasma centrale major surface protein-2 pseudogenes

2010 ◽  
Vol 143 (2-4) ◽  
pp. 277-283 ◽  
Author(s):  
T. Molad ◽  
B. Leibovich ◽  
M. Mazuz ◽  
L. Fleiderovich ◽  
L. Fish ◽  
...  
Keyword(s):  
Surface Protein ◽  
Major Surface Protein ◽  
Major Surface ◽  
Anaplasma Centrale

Three strains of Wolbachia pipientis and high rates of infection in Iranian sandfly species

2014 ◽  
Vol 104 (2) ◽  
pp. 195-202 ◽  
Author(s):  
A. Bordbar ◽  
S. Soleimani ◽  
F. Fardid ◽  
M.R. Zolfaghari ◽  
P. Parvizi
Keyword(s):  
Protein Gene ◽  
Surface Protein ◽  
Male And Female ◽  
Wolbachia Pipientis ◽  
Major Surface Protein ◽  
Zoonotic Cutaneous Leishmaniasis ◽  
Geographical Regions ◽  
Surface Protein Gene ◽  
Major Surface ◽  
Zoonotic Visceral Leishmaniasis

AbstractIndividual wild-caught sandflies from Iran were examined for infections of Wolbachia pipientis by targeting the major surface protein gene wsp of this intracellular α-proteobacterium. In total, 638 male and female sandflies were screened, of which 241 were found to be positive for one of three wsp haplotypes. Regardless of geographical origins and habitats, Phlebotomus (Phlebotomus) papatasi and other sandfly species were found to be infected with one common, widespread strain of A-group W. pipientis (Turk 54, GenBank accession EU780683; AY288297). In addition, a new A-group haplotype (Turk07, GenBank accession KC576916) was isolated from Phlebotomus (Paraphlebotomus) mongolensis and Phlebotomus (Pa.) caucasicus, and a new B-group haplotype (AZ2331, GenBank accession JX488735) was isolated from Phlebotomus (Larroussius) perfiliewi. Therefore, Wolbachia was found to occur in at least three of the incriminated vectors of zoonotic cutaneous leishmaniasis and zoonotic visceral leishmaniasis in different geographical regions of Iran. It may provide a new tool for the future control of leishmaniasis.

scholarly journals CD4+ T Lymphocytes from Calves Immunized withAnaplasma marginale Major Surface Protein 1 (MSP1), a Heteromeric Complex of MSP1a and MSP1b, Preferentially Recognize the MSP1a Carboxyl Terminus That Is Conserved among Strains

2001 ◽  
Vol 69 (11) ◽  
pp. 6853-6862 ◽  
Author(s):  
Wendy C. Brown ◽  
Guy H. Palmer ◽  
Harris A. Lewin ◽  
Travis C. McGuire
Keyword(s):  
T Lymphocytes ◽  
T Lymphocyte ◽  
Protective Immunity ◽  
B Lymphocyte ◽  
Surface Protein ◽  
Specific Response ◽  
Major Surface Protein ◽  
Ifn Γ ◽  
Major Surface ◽  
Lymphocyte Responses

ABSTRACT Native major surface protein 1 (MSP1) of the ehrlichial pathogenAnaplasma marginale induces protective immunity in calves challenged with homologous and heterologous strains. MSP1 is a heteromeric complex of a single MSP1a protein covalently associated with MSP1b polypeptides, of which at least two (designated MSP1F1 and MSP1F3) in the Florida strain are expressed. Immunization with recombinant MSP1a and MSP1b alone or in combination fails to provide protection. The protective immunity in calves immunized with native MSP1 is associated with the development of opsonizing and neutralizing antibodies, but CD4+ T-lymphocyte responses have not been evaluated. CD4+ T lymphocytes participate in protective immunity to ehrlichial pathogens through production of gamma interferon (IFN-γ), which promotes switching to high-affinity immunoglobulin G (IgG) and activation of phagocytic cells to produce nitric oxide. Thus, an effective vaccine for A. marginaleand related organisms should contain both T- and B-lymphocyte epitopes that induce a strong memory response that can be recalled upon challenge with homologous and heterologous strains. This study was designed to determine the relative contributions of MSP1a and MSP1b proteins, which contain both variant and conserved amino acid sequences, in stimulating memory CD4+ T-lymphocyte responses in calves immunized with native MSP1. Peripheral blood mononuclear cells and CD4+ T-cell lines from MSP1-immunized calves proliferated vigorously in response to the immunizing strain (Florida) and heterologous strains of A. marginale. The conserved MSP1-specific response was preferentially directed to the carboxyl-terminal region of MSP1a, which stimulated high levels of IFN-γ production by CD4+ T cells. In contrast, there was either weak or no recognition of MSP1b proteins. Paradoxically, all calves developed high titers of IgG antibodies to both MSP1a and MSP1b polypeptides. These findings suggest that in calves immunized with MSP1 heteromeric complex, MSP1a-specific T lymphocytes may provide help to MSP1b-specific B lymphocytes. The data provide a basis for determining whether selected MSP1a CD4+ T-lymphocyte epitopes and selected MSP1a and MSP1b B-lymphocyte epitopes presented on the same molecule can stimulate a protective immune response.

Sign in / Sign up

Export Citation Format

Share Document