HIV-1 gag-specific cytotoxic T lymphocytes defined with recombinant vaccinia virus and synthetic peptides

Nixon, Douglas F.; Townsend, Alain; Elvin, John; Rizza, C. R.; Gallwey, John; McMichael, Andrew J.

doi:10.1038/336484a0

Cited by 423 publications

(232 citation statements)

References 14 publications

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“…Five latent protein peptides (derived from EBNA-2, 3 and 6) gave positive results on two different MHC molecules and one (Lydma-1 derived from LMP) appeared to have a broad cross-reactivity. showing intermediate binding to all the four molecules.The peptide KRWIILGLNKIVRM has been shown to be B27 specific [34]. We now show, that the same sequence (HIV-1 gagpeptide22/23) binds toA2.1 and Kh, suggesting similar binding capacity of these human and murinc MHC molecules.…”

Section: Discussionmentioning

confidence: 51%

Assessment of major histocompatibility complex class I interaction with Epstein‐Barr virus and human immunodeficiency virus peptides by elevation of membrane H‐2 and HLA in peptide loading‐deficient cells

et al. 1992

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Earlier findings indicate that peptides can affect the expression of major histocompatibility complex (MHC) class I molecules on the surface of cells with defective peptide loading mechanism. We have used peptide induced increase of class I antigen expression to assess peptide interaction with MHC class I molecules. A panel of 41 overlapping synthetic peptides derived from the human immunodeficiency virus-1 (HIV-1) gag protein and 33 nonoverlapping peptides from Epstein-Barr virus (EBV) proteins EBNA-1, 2, 3, 4, 5 , 6, LMP, BZLF2, BILF2, BSLF2, BALF4 and BcLFl was assessed for the ability to enhance the expression of HLA-A2.1, H-2Db, Kh and Dd on the murine RMA-S and human 721.174/T2 (. 174/T2) lines by indirect immunofluorescence. Considering doubling of the fluorescence intensity in the peptide-treated samples as positivity, 6 of 39 HIVand 1 of 32 EBVpeptides were found to bind to A2.1,6 of 39 HIVgag and 7 of 16 EBVpeptides to Dh, 8 of 39 HIVgag and 5 of 16 EBV peptides to Kb and 2 of 39 HIV gag and 1 of 17 EBV peptides to Dd. The sensitivity of the method is comparable to the in vitro class I assembly assay with conformation-dependent monoclonal antibody and is more discriminating than the solid-phase assay. Due to its simplicity this method can also serve for testing large peptide panels for binding capacity to various class I molecules. Moreover, the method provides information about the relevance of in vitro tests for class I assembly in living cells.

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Section: Discussionmentioning

confidence: 51%

Assessment of major histocompatibility complex class I interaction with Epstein‐Barr virus and human immunodeficiency virus peptides by elevation of membrane H‐2 and HLA in peptide loading‐deficient cells

et al. 1992

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“…We next studied the effect of ERAP1 on presentation to CTLs of a defined immunodominant HIV-Gag HLA-B27 epitope (KRWIILGLNK, or KK10) (21). HeLa.B27 cells transduced with control shRNA or ERAP1 shRNA were infected with HIV-Gag rVV and cocultured with an HLA-B27-restricted KK10-specific CTL clone (011-B5).…”

Section: Erap1 In Hla-b27 Peptide Presentation 287mentioning

confidence: 99%

Critical Role of Endoplasmic Reticulum Aminopeptidase 1 in Determining the Length and Sequence of Peptides Bound and Presented by HLA–B27

Chen

Fischer

Peng

et al. 2014

Arthritis & Rheumatology

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Objective. HLA-B27 and endoplasmic reticulum aminopeptidase 1 (ERAP1) are the two strongest genetic factors predisposing to ankylosing spondylitis (AS). A key aminopeptidase in class I major histocompatibility complex presentation, ERAP1 potentially contributes to the pathogenesis of AS by altering HLA-B27 peptide presentation. The aim of this study was to analyze the effects of ERAP1 on the HLA-B27 peptide repertoire and peptide presentation to cytotoxic T lymphocytes (CTLs).Methods. ERAP1-silenced and -competent HeLa.B27 and C1R.B27 cells were isotope-labeled, mixed, lysed, and then immunoprecipitated using W6/32 or ME1 antibodies. Peptides bound to HLA-B27 were eluted and analyzed by tandem mass spectrometry. Selected peptides were synthesized and tested for HLA-B27 binding ability. The effect of ERAP1 silencing/ mutation on presentation of an immunodominant viral HLA-B27 epitope, KK10, to CTLs was also studied.Results. In both HeLa.B27 and C1R.B27 cells, the proportion of 9-mer HLA-B27-bound peptides was decreased by ERAP1 silencing, whereas the percentages of longer peptides (11-13 mer) were increased. Surprisingly, following ERAP1 silencing, C-terminally extended peptides were readily identified. These were better able to bind to HLA-B27 than were N-terminally extended peptides lacking an arginine at position 2. In both HeLa.B27 cells and mouse fibroblasts expressing HLA-B27, the absence of ERAP1 reduced peptide recognition by HLA-B27-restricted KK10-specific CTLs following infection with recombinant vaccinia virus or transfection with minigenes expressing KK10 precursors. Presence of an AS-protective variant of ERAP1, K528R, as compared to wild-type ERAP1, reduced the peptide recognition by KK10 CTLs following transfection with extended KK10 minigenes.Conclusion. These results show that ERAP1 directly alters peptide binding and presentation by HLA-B27, thus demonstrating a potential pathogenic mechanism in AS. Inhibition of ERAP1 could potentially be used for treatment of AS and other ERAP1-associated diseases.The human leukocyte antigen HLA-B27 is very strongly associated with development of the common inflammatory rheumatic disease ankylosing spondylitis (AS). However, the pathogenic mechanism remains unclear. Recent genome-wide association studies have identified additional AS-associated genes, of which the strongest association is with endoplasmic reticulum aminopeptidase 1 (ERAP1) (1). The strong genetic association of AS with ERAP1 single-nucleotide polymorphisms has been confirmed in different populations (2-7).

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“…This list is proportionately much smaller considering the relative number of alleles involved and this reflects the effort spent in defining new epitopes in these patients, rather than the importance of such responses. It is not clear whether, unlike HLA-A2, one peptide may be immunodominant if a particular restriction element is present as for HLA-B27 in HIV [61]. Much more work needs to be done in this area before any strong conclusions can be drawn.…”

Section: Hcv-specific Epitopes -The Evidence Basementioning

confidence: 99%

Cellular immune responses against hepatitis C virus: the evidence base 2002

Ward¹,

Lauer

Isba³

et al. 2002

Clinical and Experimental Immunology

141

102

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SUMMARYHepatitis C virus (HCV) is an RNA virus which is estimated to persistently infect about 170 million people worldwide. After acute infection, there is an initial period during which long-term outcome is decided. There is strong evidence that the cellular immune responses, involving both CD4 + and CD8 + T lymphocytes, are involved at this stage and it is their effectiveness which determines outcome. What is not understood is what determines their effectiveness. The most important component of this is likely to be some aspect of epitope selection, itself dictated by host MHC. Thus, to understand host immunity to HCV, we need to have a detailed understanding of the peptides involved in T lymphocyte responses. In this review, we discuss the peptide epitopes that have been identified so far, and their potential significance. We relate this to a scheme of host defence which may be useful for understanding natural and vaccine-induced immunity.

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HIV-1 gag-specific cytotoxic T lymphocytes defined with recombinant vaccinia virus and synthetic peptides

Cited by 423 publications

References 14 publications

Assessment of major histocompatibility complex class I interaction with Epstein‐Barr virus and human immunodeficiency virus peptides by elevation of membrane H‐2 and HLA in peptide loading‐deficient cells

Assessment of major histocompatibility complex class I interaction with Epstein‐Barr virus and human immunodeficiency virus peptides by elevation of membrane H‐2 and HLA in peptide loading‐deficient cells

Critical Role of Endoplasmic Reticulum Aminopeptidase 1 in Determining the Length and Sequence of Peptides Bound and Presented by HLA–B27

Cellular immune responses against hepatitis C virus: the evidence base 2002

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