The Epitopes of Influenza Nucleoprotein Recognized by Cytotoxic T Lymphocytes Can Be Defined with Short Synthetic Peptides

Townsend, Alain; Rothbard, Jonathan B.; Gotch, Frances; Bastin, Judy; Bahadur, Gulam; Wraith, David C; McMichael, Andrew J.

doi:10.1016/b978-0-12-551855-0.50101-7

Cited by 90 publications

(98 citation statements)

References 8 publications

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“…36). Peptide fragments presented on the surface of antigen-presenting cells in the context of MHC class II molecules are recognized by CD4+ T cells (1)(2)(3)(4)(5). In the endogenous pathway, peptide fragments of protein antigens presented in MHC class I molecules to CD8+ T cells are generally derived from intracellular host proteins or proteins of intracellular infectious agents (1)(2)(3)(4)(5).…”

Section: Tl-sp1omn(a) and F-t1-sp1omn(a) Peptides Prime Cd8+mentioning

confidence: 99%

“…In contrast, viral soluble proteins and synthetic peptides generally do not induce CTLs in vivo (2,(4)(5)(6). Recently, it has been suggested that viral infection of the host may not always be required for CD8' CTL generation, as examples of in vivo priming of CD8' CTLs with derivatized or free synthetic peptides have been reported (7)(8)(9)(10)(11) In prior work, we synthesized a HIV env gpl20 T-cell epitope (Ti) (12) N-terminal to hydrophilic gpl20 B-cell epitopes from the V3 loop region (SP10 sequences) (13)(14)(15).…”

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confidence: 99%

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Priming of anti-human immunodeficiency virus (HIV) CD8+ cytotoxic T cells in vivo by carrier-free HIV synthetic peptides.

Hart

Weinhold

Scearce

et al. 1991

Proc. Natl. Acad. Sci. U.S.A.

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Section: Tl-sp1omn(a) and F-t1-sp1omn(a) Peptides Prime Cd8+mentioning

confidence: 99%

mentioning

confidence: 99%

Priming of anti-human immunodeficiency virus (HIV) CD8+ cytotoxic T cells in vivo by carrier-free HIV synthetic peptides.

Hart

Weinhold

Scearce

et al. 1991

Proc. Natl. Acad. Sci. U.S.A.

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“…In population studies, sequence comparison of these otherwise serologically similar HLA molecules (9), exon shuffling (10,11), and site-directed mutagenesis (12)(13)(14)(15) have all highlighted the importance of polymorphic residues in the a1 and/or a2 domains of the HLA molecule in the recognition process. Moreover, the class I MHC molecules were shown to present peptides derived from processed antigens to the receptor of cytotoxic T cells (16,17). Elucidation ofthe crystal structure ofHLA-A2 revealed a platform ofeight antiparallel (3 strands topped by two a-helices (18,19).…”

mentioning

confidence: 99%

Alloreactivity studied with mutants of HLA-A2.

Santos-Aguado

Crimmins

Mentzer

et al. 1989

Proc. Natl. Acad. Sci. U.S.A.

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Based on the crystal structure of HLA-A2.1 and the recognition of a panel of mutant HLA-A2.1 molecules by a large number of alloreactive cytotoxic T lymphocyte clones, a model to explain alloreactivity is described. In this model recognition of an allogeneic major histocompatibility complex molecule by a self-restricted T-cell receptor occurs as the result ofaccommodation by the receptor ofa few amino acid differences in the major histocompatibility complex moleculei.e., cross-recognition. Alloreactivity is the result of the presence in the foreign antigen binding site of the allogeneic major histocompatibility complex molecule of unusual self-peptides, reactivity to which could not have been eliminated by negative thymic selection.Class I major histocompatibility complex (MHC) molecules (HLA molecules in man) were originally identified as the target structures responsible for the humoral (alloantibody) and cellular (alloreactive cytotoxic T lymphocyte) responses generated during the rejection of transplanted foreign tissue (1). However, the central role of these highly polymorphic cellsurface glycoproteins is to serve as restricting elements in the recognition by T cells of virus-infected, chemically modified, or neoplastic cells (2-5). The regions in contact between the molecules involved in the recognition process (T-cell receptor, class I MHC molecule, peptide, and accessory molecules) are not yet precisely described, and the nature and and biophysical characteristics of these interactions (6) remain to be determined. Identification of specific residues on class I MHC molecules involved in the recognition by human cytotoxic T lymphocytes (CTL) has been facilitated over the last few years by the structural characterization of natural HLA variants initially distinguished by cytotoxicity assays (7) and/or isoelectric focusing (8). In population studies, sequence comparison of these otherwise serologically similar HLA molecules (9), exon shuffling (10,11), and site-directed mutagenesis (12)(13)(14)(15) have all highlighted the importance of polymorphic residues in the a1 and/or a2 domains of the HLA molecule in the recognition process. Moreover, the class I MHC molecules were shown to present peptides derived from processed antigens to the receptor of cytotoxic T cells (16, 17). Elucidation ofthe crystal structure ofHLA-A2 revealed a platform ofeight antiparallel (3 strands topped by two a-helices (18,19). A prominent groove between the helices was identified as the site for binding of foreign peptides.In the present study, site-directed mutagenesis of HLA-A2

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“…It is believed that the antigen receptor of cytotoxic T cells restricted by class I MHC products recognises antigenic peptides in association with the restriction element (75). Moreover, there is evidence from the study of influenza virusspecific cytotoxic T cells in mice and humans that this association may be the result of the processing of endogenously synthesised antigens (50,73).…”

Section: Parasite Strain Specificitymentioning

confidence: 99%

“…This is not surprising in view of the current perception of the interaction between the T cell receptor and its ligand. As already mentioned, it is believed that T cells recognise processed rather than native antigen, and there is evidence that synthetic peptides of only 13-16 amino acids are sufficient in length to span T cell epitopes of influenza nucleoprotein (8,75). Indeed, the antigen binding cleft described by Bjorkman et al (11) between the first and second domains of the class I MHC molecule can accomodate only 20 amino acids.…”

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confidence: 99%

Theileria parva : the nature of the immune response and its significance for immunoprophylaxis

McKeever¹,

Morrison²

1990

Rev. Sci. Tech. OIE

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Summary: Theileria parva is a tick-borne haemoprotozoan parasite of cattle and buffalo which is responsible for considerable economic losses to cattle farming in Eastern, Central and Southern Africa. Infection with the parasite results in an acute lymphoproliferative disorder with high mortality, but animals which survive infection are solidly immune to homologous challenge. Such immunity can be reproduced by infecting cattle with the parasite and treating them with tetracyclines or theilericidal drugs, but the widespread use of this technique as a method of control is hindered by its dependence on live parasites which require cryopreservation for maintenance and can give rise to carrier States. In addition, cross-protection between different strains of the parasite is not absolute. These problems have prompted a search for methods of immunisation based on the use of inactivated parasites or their derivatives. Such efforts have met with consistent failure, however, and in recent years scientists have adopted the more rational approach of defining the immune responses of cattle to the parasite with a view to identifying the parasite components which provoke them. These studies have revealed that protection is likely to be mediated by parasitespecific cytotoxic T cells which are restricted by class I major histocompatibility complex (MHC) products. The significance of this observation to the development of an effective subunit vaccine is discussed in the light of current knowledge of the inductive requirements of cytotoxic T cells.KEYWORDS: Antibody -Antigen -Antigen delivery -Antigen processingCell-mediated immunity -Cross-protection -Immunisation -Immunity -MHCrestriction -Parasite -Pathology -Theileria -Vaccine. THE PARASITE AND ITS LIFE CYCLETheileria parva is a haemoprotozoan parasite which infects cattle and buffalo in large areas of Eastern, Central and Southern Africa. The sporozoite stage of the parasite is transmitted by the three-host tick Rhipicephalus appendiculatus and invades lymphocytes, where its development to the schizont stage is associated with uncontrolled proliferation of the cell. The capacity of the parasite to associate with the mitotic spindle (78) ensures that schizonts are passed on to successive generations of daughter cells, giving rise to a clonal expansion of the initially parasitised population. A proportion of parasitised cells undergo merogony, resulting in disruption of the lymphocyte and release of merozoites into the blood. Merozoites then invade erythrocytes and differentiate into piroplasms which constitute the infective stage for the tick. PATHOGENESISInfection of cattle with T. parva gives rise to an acute lymphoproliferative disorder known as East Coast fever (ECF), and the course of this disease has been well characterised in experimentally-infected animals (47). At approximately 8 days after infection, schizont-infected cells are detectable in the lymph node which drains the site of inoculation. Parasitised cells can be detected in other lymphoid tissues throughout th...

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The Epitopes of Influenza Nucleoprotein Recognized by Cytotoxic T Lymphocytes Can Be Defined with Short Synthetic Peptides

Cited by 90 publications

References 8 publications

Priming of anti-human immunodeficiency virus (HIV) CD8+ cytotoxic T cells in vivo by carrier-free HIV synthetic peptides.

Priming of anti-human immunodeficiency virus (HIV) CD8+ cytotoxic T cells in vivo by carrier-free HIV synthetic peptides.

Alloreactivity studied with mutants of HLA-A2.

Theileria parva : the nature of the immune response and its significance for immunoprophylaxis

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