The epitopes of influenza nucleoprotein recognized by cytotoxic T lymphocytes can be defined with short synthetic peptides

doi:10.1016/0092-8674(86)90019-X

Cell

Volume 44, Issue 6, 28 March 1986, Pages 959-968

https://doi.org/10.1016/0092-8674(86)90019-X Get rights and content

Abstract

A proportion of cytotoxic T lymphocytes (CTL) responding to infection by influenza recognize target cells that express the viral nucleoprotein. Recent work showed that CTL can recognize short overlapping regions of large nucleoprotein fragments expressed in transfected L cells. This led to the suggestion that CTL recognize segmental epitopes of denatured or degraded proteins in a similar way to helper T cells. One corollary of this idea is that CTL should recognize appropriate short peptides on the target cell surface. We demonstrate that the epitopes of nucleoprotein recognized by CTL in association with class I molecules of the major histocompatibility complex in both mouse and man can be defined with short synthetic peptides derived from the nucleoprotein sequence.

References (43)

H.M. Grey et al.
Antigen processing and presentation to T cells
Immunol. Today
(1985)
D.R. Kaplan et al.
Influenza virus-specific human cytotoxic T cell clones: heterogeneity in antigenic specificity and restriction by Class II MHC products
Cell. Immunol.
(1984)
M.D. Lubeck et al.
Non-random association of parental genes in influenza A virus recombinants
Virology
(1979)
S.L. Swain et al.
Mouse T lymphocyte subpopulations: relationships between function and Lyt antigen phenotype
Immunol. Today
(1980)
A.R.M. Townsend et al.
Cytotoxic T cell recognition of the influenza nucleoprotein and hemagglutinin expressed in transfected mouse L cells
Cell
(1984)
A.R.M. Townsend et al.
Recognition of influenza A virus nucleoprotein by an H-2 restricted cytotoxic T-cell clone
Virology
(1984)
A.R.M. Townsend et al.
Cytotoxic T cells recognize fragments of influenza nucleoprotein
Cell
(1985)
G. Winter et al.
The structure of the gene encoding the nucleoprotein of human influenza virus A/PR/8/34
Virology
(1981)
R.M. Zinkernagel et al.
MHC-restricted cytotoxic T cells: studies on the biological role of polymorphic major transplantation antigens determining T cell restriction specificity, function, and responsiveness
Adv. Immunol.
(1979)
P.M. Allen et al.
Specificity of the T cell receptor: two different determinants are generated by the same peptide and the I-A^k molecule
J. Immunol.
(1985)

B.A. Askonas et al.

The immune response to influenza viruses and the problem of protection against infection

B.P. Babbitt et al.

Binding of immunogenic peptides to la histocompatibility molecules

Nature

(1985)

M. Baez et al.

Gene composition of high yielding influenza vaccine strains obtained by recombination

J. Infect. Dis.

(1980)

B. Benacerraf

A hypothesis to relate the specificity of T lymphocytes and the activity of I region-specific Ir genes in macrophages and B lymphocytes

J. Immunol.

(1978)

R.V. Blanden et al.

Genes required for cytotoxicity against virus-infected target cells in K and D regions of H-2 complex

Nature

(1975)

R.V. Blanden et al.

Different D end-dependent antigenic determinants are recognised by H-2 restricted cytotoxic T cells specific for influenza and bebaru virus

J. Exp. Med.

(1979)

C. De Lisi et al.

T-cell antigenic sites tend to be amphipathic structures

D.P. Dialynas et al.

Characterisation of the murine antigenic determinant L3T4a, recognised by monoclonal antibody GK1.5: expression of L3T4a by functional T cell clones appears to correlate primarily with Class II MHC antigen-reactivity

Immunol. Rev.

(1983)

B. Fleischer et al.

Recognition of viral antigens by human influenza A virus-specific T lymphocyte clones

J. Immunol.

(1985)

C.J. Hackett et al.

Influenza virus site recognized by a murine helper T cell specific for H1 strains: localisation to a nine amino acid sequence in the hemagglutinin molecule

J. Exp. Med.

(1983)

E. Heber-Katz et al.

Contribution of antigen-presenting cell major histocompatibility complex gene products to the specificity of antigen-induced T cell activation

J. Exp. Med.

(1982)

Cited by (1491)

How mass spectrometric interrogation of MHC class I ligandomes has advanced our understanding of immune responses to viruses
2023, Seminars in Immunology
Pathways of MHC I cross-presentation of exogenous antigens
2023, Seminars in Immunology
Phagocytes, particularly dendritic cells (DCs), generate peptide-major histocompatibility complex (MHC) I complexes from antigens they have collected from cells in tissues and report this information to CD8 T cells in a process called cross-presentation. This process allows CD8 T cells to detect, respond and eliminate abnormal cells, such as cancers or cells infected with viruses or intracellular microbes. In some settings, cross-presentation can help tolerize CD8 T cells to self-antigens. One of the principal ways that DCs acquire tissue antigens is by ingesting this material through phagocytosis. The resulting phagosomes are key hubs in the cross-presentation (XPT) process and in fact experimentally conferring the ability to phagocytize antigens can be sufficient to allow non-professional antigen presenting cells (APCs) to cross-present. Once in phagosomes, exogenous antigens can be cross-presented (XPTed) through three distinct pathways. There is a vacuolar pathway in which peptides are generated and then bind to MHC I molecules within the confines of the vacuole. Ingested exogenous antigens can also be exported from phagosomes to the cytosol upon vesicular rupture and/or possibly transport. Once in the cytosol, the antigen is degraded by the proteasome and the resulting oligopeptides can be transported to MHC I molecule in the endoplasmic reticulum (ER) (a phagosome-to-cytosol (P2C) pathway) or in phagosomes (a phagosome-to-cytosol-to-phagosome (P2C2P) pathway). Here we review how phagosomes acquire the necessary molecular components that support these three mechanisms and the contribution of these pathways. We describe what is known as well as the gaps in our understanding of these processes.
MHC Class I Immunopeptidome: Past, Present, and Future
2022, Molecular and Cellular Proteomics
In the 35 years since the revelation that short peptides bound to major histocompatibility complex class I and II molecules are the secret of the major histocompatibility complex–restricted nature of T-cell recognition, there has been enormous progress in characterizing the immunopeptidome, the repertoire of peptide presented for immunosurveillance. Here, the major milestones in the journey are marked, the contribution of proteasome-mediated splicing to the immunopeptidome is discussed, and exciting recent findings relating the immunopeptidome to the translatome revealed by ribosome profiling (RiboSeq) is detailed. Finally, what is needed for continued progress is opined about, which includes the infusion of talented young scientists into the antigen-processing field, currently undergoing a renaissance; thanks in part to the astounding success of T-cell–based cancer immunotherapy.
Effect of epitope variant co-delivery on the depth of CD8 T cell responses induced by HIV-1 conserved mosaic vaccines
2021, Molecular Therapy Methods and Clinical Development
Citation Excerpt :
If this vaccine strategy proves effective, the vaccine’s cross-clade reach offers a global deployment. CD8+ killer T cells recognize HIV-1 epitopes of 8–12 aa (most commonly 9) presented by major histocompatibility complex (MHC) class I molecules.12,13 Even the most conserved regions of HIV-1 proteins retain at the epitope level a degree of variability.14
To stop the HIV-1 pandemic, vaccines must induce responses capable of controlling vast HIV-1 variants circulating in the population as well as those evolved in each individual following transmission. Numerous strategies have been proposed, of which the most promising include focusing responses on the vulnerable sites of HIV-1 displaying the least entropy among global isolates and using algorithms that maximize vaccine match to circulating HIV-1 variants by vaccine cocktails of optimized complementing sequences. In this study, we investigated CD8 T cell responses induced by a bi-valent mosaic of highly conserved HIVconsvX regions delivered by a combination of simian adenovirus ChAdOx1 and poxvirus MVA. We compared partially and fully mono- and bi-valent prime-boost regimens and their ability to elicit T cells recognizing natural epitope variants using an interferon-γ enzyme-linked immunospot (ELISPOT) assay. We used 11 well-defined CD8 T cell epitopes in two mouse haplotypes and, for each epitope, assessed recognition of the two vaccine forms together with the other most frequent epitope variants in the HIV-1 database. We conclude that for the magnitude and depth of epitope recognition, CD8 T cell responses benefitted in most comparisons from the combined bi-valent mosaic and envisage the main advantage of the bi-valent vaccine during its deployment to diverse populations.
50 Years of structural immunology
2021, Journal of Biological Chemistry
Fifty years ago, the first landmark structures of antibodies heralded the dawn of structural immunology. Momentum then started to build toward understanding how antibodies could recognize the vast universe of potential antigens and how antibody-combining sites could be tailored to engage antigens with high specificity and affinity through recombination of germline genes (V, D, J) and somatic mutation. Equivalent groundbreaking structures in the cellular immune system appeared some 15 to 20 years later and illustrated how processed protein antigens in the form of peptides are presented by MHC molecules to T cell receptors. Structures of antigen receptors in the innate immune system then explained their inherent specificity for particular microbial antigens including lipids, carbohydrates, nucleic acids, small molecules, and specific proteins. These two sides of the immune system act immediately (innate) to particular microbial antigens or evolve (adaptive) to attain high specificity and affinity to a much wider range of antigens. We also include examples of other key receptors in the immune system (cytokine receptors) that regulate immunity and inflammation. Furthermore, these antigen receptors use a limited set of protein folds to accomplish their various immunological roles. The other main players are the antigens themselves. We focus on surface glycoproteins in enveloped viruses including SARS-CoV-2 that enable entry and egress into host cells and are targets for the antibody response. This review covers what we have learned over the past half century about the structural basis of the immune response to microbial pathogens and how that information can be utilized to design vaccines and therapeutics.
Before Virus, After Virus: A Reckoning
2020, Cell
The 2020 Lasker Awards, a celebration of one of the most prestigious international prizes given to individuals for extraordinary contributions to Basic and Clinical Medical Research, Public Health, and Special Achievement, was cancelled because of the COVID-19 pandemic. Typically, essays on the awardees and their scientific and medical contributions are solicited and published in Cell in collaboration with the Lasker Committee. This year, the Lasker Committee commissioned an essay to reflect on the historic contributions that scientists and physicians have made to our understanding of immunology and virology, and future directions in medical and basic research that have been highlighted by COVID-19 pandemic.

View all citing articles on Scopus

View full text

Cell

ArticleThe epitopes of influenza nucleoprotein recognized by cytotoxic T lymphocytes can be defined with short synthetic peptides

Abstract

Immunol. Today

Cell. Immunol.

Virology

Immunol. Today

Cell

Virology

Cell

Virology

Adv. Immunol.

Specificity of the T cell receptor: two different determinants are generated by the same peptide and the I-Ak molecule

J. Immunol.

The immune response to influenza viruses and the problem of protection against infection

Binding of immunogenic peptides to la histocompatibility molecules

Nature

Gene composition of high yielding influenza vaccine strains obtained by recombination

J. Infect. Dis.

A hypothesis to relate the specificity of T lymphocytes and the activity of I region-specific Ir genes in macrophages and B lymphocytes

J. Immunol.

Genes required for cytotoxicity against virus-infected target cells in K and D regions of H-2 complex

Nature

Different D end-dependent antigenic determinants are recognised by H-2 restricted cytotoxic T cells specific for influenza and bebaru virus

J. Exp. Med.

T-cell antigenic sites tend to be amphipathic structures

Characterisation of the murine antigenic determinant L3T4a, recognised by monoclonal antibody GK1.5: expression of L3T4a by functional T cell clones appears to correlate primarily with Class II MHC antigen-reactivity

Immunol. Rev.

Recognition of viral antigens by human influenza A virus-specific T lymphocyte clones

J. Immunol.

Influenza virus site recognized by a murine helper T cell specific for H1 strains: localisation to a nine amino acid sequence in the hemagglutinin molecule

J. Exp. Med.

Contribution of antigen-presenting cell major histocompatibility complex gene products to the specificity of antigen-induced T cell activation

J. Exp. Med.

Article
The epitopes of influenza nucleoprotein recognized by cytotoxic T lymphocytes can be defined with short synthetic peptides

Specificity of the T cell receptor: two different determinants are generated by the same peptide and the I-A^k molecule