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Tuning antiviral CD...
Tuning antiviral CD8 T-cell response via proline-altered peptide ligand vaccination
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- Duru, Adil Doganay (författare)
- Karolinska Inst, Dept Med Solna, Sci Life Lab, Stockholm, Sweden.;Karolinska Univ Hosp, Div Infect Dis, Stockholm, Sweden.;Nova Southeastern Univ, NSU Cell Therapy Inst, Ft Lauderdale, FL 33314 USA.;Nova Southeastern Univ, Kiran C Patel Coll Allopath Med, Ft Lauderdale, FL 33314 USA.
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- Sun, Renhua (författare)
- Karolinska Institutet
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- Allerbring, Eva B. (författare)
- Karolinska Inst, Dept Med Solna, Sci Life Lab, Stockholm, Sweden.;Karolinska Univ Hosp, Div Infect Dis, Stockholm, Sweden.
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- Chadderton, Jesseka (författare)
- Monash Univ, Biomed Discovery Inst, Dept Microbiol, Clayton, Vic, Australia.
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- Kadri, Nadir (författare)
- Karolinska Institutet
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- Han, Xiao (författare)
- Karolinska Institutet
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- Peqini, Kaliroi (författare)
- Univ Milan, Sez Chim Gen & Organ, Dipartimento Sci Farmaceut, DISFARM, Milan, Italy.
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- Uchtenhagen, Hannes (författare)
- Karolinska Inst, Dept Med Solna, Sci Life Lab, Stockholm, Sweden.;Karolinska Univ Hosp, Div Infect Dis, Stockholm, Sweden.
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- Madhurantakam, Chaithanya (författare)
- Karolinska Inst, Dept Med Solna, Sci Life Lab, Stockholm, Sweden.;Karolinska Univ Hosp, Div Infect Dis, Stockholm, Sweden.;TERI, Dept Biotechnol, Struct & Mol Biol Lab, Sch Adv Studies, New Delhi, India.
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- Pellegrino, Sara (författare)
- Univ Milan, Sez Chim Gen & Organ, Dipartimento Sci Farmaceut, DISFARM, Milan, Italy.
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- Sandalova, Tatyana (författare)
- Karolinska Institutet
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- Nygren, Per-Åke, 1961- (författare)
- KTH,Proteinvetenskap
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- Turner, Stephen J. (författare)
- Monash Univ, Biomed Discovery Inst, Dept Microbiol, Clayton, Vic, Australia.
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- Achour, Adnane (författare)
- Karolinska Institutet
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Karolinska Institutet Karolinska Inst, Dept Med Solna, Sci Life Lab, Stockholm, Sweden;Karolinska Univ Hosp, Div Infect Dis, Stockholm, Sweden.;Nova Southeastern Univ, NSU Cell Therapy Inst, Ft Lauderdale, FL 33314 USA.;Nova Southeastern Univ, Kiran C Patel Coll Allopath Med, Ft Lauderdale, FL 33314 USA. (creator_code:org_t)
- 2020-05-04
- 2020
- Engelska.
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Ingår i: PLoS Pathogens. - : PUBLIC LIBRARY SCIENCE. - 1553-7366 .- 1553-7374. ; 16:5
- Relaterad länk:
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https://doi.org/10.1...
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https://journals.plo...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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http://kipublication...
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Abstract
Ämnesord
Stäng
- Viral escape from CD8(+) cytotoxic T lymphocyte responses correlates with disease progression and represents a significant challenge for vaccination. Here, we demonstrate that CD8(+) T cell recognition of the naturally occurring MHC-I-restricted LCMV-associated immune escape variant Y4F is restored following vaccination with a proline-altered peptide ligand (APL). The APL increases MHC/peptide (pMHC) complex stability, rigidifies the peptide and facilitates T cell receptor (TCR) recognition through reduced entropy costs. Structural analyses of pMHC complexes before and after TCR binding, combined with biophysical analyses, revealed that although the TCR binds similarly to all complexes, the p3P modification alters the conformations of a very limited amount of specific MHC and peptide residues, facilitating efficient TCR recognition. This approach can be easily introduced in peptides restricted to other MHC alleles, and can be combined with currently available and future vaccination protocols in order to prevent viral immune escape. Author summary Viral escape mutagenesis correlates often with disease progression and represents a major hurdle for vaccination-based therapies. Here, we have designed and developed a novel generation of altered epitopes that re-establish and enhance significantly CD8(+) T cell recognition of a naturally occurring viral immune escape variant. Biophysical and structural analyses provide a clear understanding of the molecular mechanisms underlying this reestablished recognition. We believe that this approach can be implemented to currently available or novel vaccination approaches to efficiently restore T cell recognition of virus escape variants to control disease progression.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
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- ref (ämneskategori)
- art (ämneskategori)
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- Av författaren/redakt...
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Duru, Adil Dogan ...
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Sun, Renhua
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Allerbring, Eva ...
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Chadderton, Jess ...
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Kadri, Nadir
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Han, Xiao
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visa fler...
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Peqini, Kaliroi
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Uchtenhagen, Han ...
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Madhurantakam, C ...
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Pellegrino, Sara
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Sandalova, Tatya ...
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Nygren, Per-Åke, ...
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Turner, Stephen ...
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Achour, Adnane
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- MEDICIN OCH HÄLSOVETENSKAP
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PLoS Pathogens
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Kungliga Tekniska Högskolan
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Karolinska Institutet