scholarly journals Identification of T Cell Epitopes on the 33-kDa Fragment ofPlasmodium yoeliiMerozoite Surface Protein 1 and Their Antibody-Independent Protective Role in Immunity to Blood Stage Malaria

2002 ◽  
Vol 169 (2) ◽  
pp. 944-951 ◽  
Author(s):  
Jiraprapa Wipasa ◽  
Chakrit Hirunpetcharat ◽  
Yuvadee Mahakunkijcharoen ◽  
Huji Xu ◽  
Salenna Elliott ◽  
...  
Keyword(s):  
T Cell ◽  
Surface Protein ◽  
Protective Role ◽  
Blood Stage ◽  
T Cell Epitopes ◽  
Blood Stage Malaria

scholarly journals Identification of Promiscuous African Swine Fever Virus T-Cell Determinants Using a Multiple Technical Approach

Vaccines ◽  
2021 ◽  
Vol 9 (1) ◽  
pp. 29
Author(s):  
Laia Bosch-Camós ◽  
Elisabet López ◽  
María Jesús Navas ◽  
Sonia Pina-Pedrero ◽  
Francesc Accensi ◽  
...  
Keyword(s):  
T Cell ◽  
Mononuclear Cells ◽  
African Swine Fever Virus ◽  
African Swine Fever ◽  
Cd8 T Cell ◽  
Protective Role ◽  
Full Length ◽  
T Cell Epitopes ◽  
Peripheral Blood Mononuclear

The development of subunit vaccines against African swine fever (ASF) is mainly hindered by the lack of knowledge regarding the specific ASF virus (ASFV) antigens involved in protection. As a good example, the identity of ASFV-specific CD8+ T-cell determinants remains largely unknown, despite their protective role being established a long time ago. Aiming to identify them, we implemented the IFNγ ELISpot as readout assay, using as effector cells peripheral blood mononuclear cells (PBMCs) from pigs surviving experimental challenge with Georgia2007/1. As stimuli for the ELISpot, ASFV-specific peptides or full-length proteins identified by three complementary strategies were used. In silico prediction of specific CD8+ T-cell epitopes allowed identifying a 19-mer peptide from MGF100-1L, as frequently recognized by surviving pigs. Complementarily, the repertoire of SLA I-bound peptides identified in ASFV-infected porcine alveolar macrophages (PAMs), allowed the characterization of five additional SLA I-restricted ASFV-specific epitopes. Finally, in vitro stimulation studies using fibroblasts transfected with plasmids encoding full-length ASFV proteins, led to the identification of MGF505-7R, A238L and MGF100-1L as promiscuously recognized antigens. Interestingly, each one of these proteins contain individual peptides recognized by surviving pigs. Identification of the same ASFV determinants by means of such different approaches reinforce the results presented here.

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 Promiscuous T-cell epitopes of Plasmodium merozoite surface protein 9 (PvMSP9) induces IFN-γ and IL-4 responses in individuals naturally exposed to malaria in the Brazilian Amazon

Vaccine ◽  
2010 ◽  
Vol 28 (18) ◽  
pp. 3185-3191 ◽  
Author(s):  
J.C. Lima-Junior ◽  
D.M. Banic ◽  
T.M. Tran ◽  
V.S.E. Meyer ◽  
S.G. De-Simone ◽  
...  
Keyword(s):  
T Cell ◽  
Surface Protein ◽  
Brazilian Amazon ◽  
Merozoite Surface Protein ◽  
T Cell Epitopes ◽  
Ifn Γ

scholarly journals Hepcidin Is Regulated during Blood-Stage Malaria and Plays a Protective Role in Malaria Infection

2011 ◽  
Vol 187 (12) ◽  
pp. 6410-6416 ◽  
Author(s):  
Hai-Zhen Wang ◽  
Ying-Xin He ◽  
Chun-Ju Yang ◽  
Wei Zhou ◽  
Cheng-Gang Zou
Keyword(s):  
Malaria Infection ◽  
Protective Role ◽  
Blood Stage ◽  
Blood Stage Malaria

Prediction of T cell epitopes of Brucella abortus and evaluation of their protective role in mice

2015 ◽  
Vol 99 (18) ◽  
pp. 7625-7637 ◽  
Author(s):  
Prachiti Afley ◽  
Sudhir K. Dohre ◽  
G. B. K. S. Prasad ◽  
Subodh Kumar
Keyword(s):  
T Cell ◽  
Brucella Abortus ◽  
Protective Role ◽  
T Cell Epitopes

scholarly journals Transient Deficiency of Dendritic Cells Results in Lack of a Merozoite Surface Protein 1-Specific CD4 T Cell Response during Peak Plasmodium chabaudi Blood-Stage Infection

2012 ◽  
Vol 80 (12) ◽  
pp. 4248-4256 ◽  
Author(s):  
Anne-Marit Sponaas ◽  
Nikolai Belyaev ◽  
Mika Falck-Hansen ◽  
Alexandre Potocnik ◽  
Jean Langhorne
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
T Cell Response ◽  
Blood Stage ◽  
Cd4 T Cell ◽  
Blood Stage Infection ◽  
Stage Infection

ABSTRACTSplenic dendritic cells are crucial for controlling the immune response to malaria by initiating a CD4 gamma interferon (IFN-γ) response early in a blood-stage infection, which contributes to parasite clearance as well as to acute-stage immunopathology. CD8−CD11chighdendritic cells have been described previously to be important antigen-presenting cells for induction of these CD4 T cell responses in the spleens ofPlasmodium chabaudi-infected mice. However, when isolated during the period of maximum parasitemia and shortly thereafter, the dendritic cells transiently lose their ability to stimulate T cells, recovering only as the parasitemia is controlled. This loss of a CD4 T cell response is also observedin vivoduring this part of the infection. CD4 T cells from a T cell receptor-transgenic mouse recognizing a peptide of merozoite surface protein 1 (MSP1) injected into BALB/c mice during peak parasitemia proliferate poorly, and very few cells produce IFN-γ and interleukin-2 (IL-2), compared with transgenic T cells injected earlier in the blood-stage infection. CD8−dendritic cells at day 10 can process and present peptides on major histocompatibility complex (MHC) class II with an efficiency similar to that of dendritic cells from earlier in infection. The failure of the day 10 dendritic cells to activate MSP1-specific CD4 T cells fullyin vitrois associated with reduced expression of CD86 and lower production of IL-12 rather than with induction of inhibitory DC receptors or production of IL-10.

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.

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.

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