Effects of a Single Escape Mutation on T Cell and HIV-1 Co-adaptation

Sun, Xiaoming; Shi, Yi; Akahoshi, Tomohiro; Fujiwara, Mamoru; Gatanaga, Hiroyuki; Schönbach, Christian; Kuse, Nozomi; Appay, Victor; Gao, George F.; Oka, Shinichi; Takiguchi, Masafumi

doi:10.1016/j.celrep.2016.05.017

Cited by 20 publications

(26 citation statements)

References 59 publications

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“…Within the vaccinated population, the HLA A * 02 genotype was a marker for success, with A * 02 + individuals showing significantly greater protection than A * 02 − individuals (54 vs. 3% effective). Other studies have made similar observations (237,238). These results not only illuminate the importance of making HLA-targeting considerations in the PBV design process, but also indicate how impactful MHC escape mutations can be when using PBVs to protect against AVPs (even when only one set of HLA-specific epitopes is affected).…”

Section: Pbv Targeting Strategies For Antigenically Variable Pathogensupporting

confidence: 66%

Designs of Antigen Structure and Composition for Improved Protein-Based Vaccine Efficacy

et al. 2020

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Today, vaccinologists have come to understand that the hallmark of any protective immune response is the antigen. However, it is not the whole antigen that dictates the immune response, but rather the various parts comprising the whole that are capable of influencing immunogenicity. Protein-based antigens hold particular importance within this structural approach to understanding immunity because, though different molecules can serve as antigens, only proteins are capable of inducing both cellular and humoral immunity. This fact, coupled with the versatility and customizability of proteins when considering vaccine design applications, makes protein-based vaccines (PBVs) one of today's most promising technologies for artificially inducing immunity. In this review, we follow the development of PBV technologies through time and discuss the antigen-specific receptors that are most critical to any immune response: pattern recognition receptors, B cell receptors, and T cell receptors. Knowledge of these receptors and their ligands has become exceptionally valuable in the field of vaccinology, where today it is possible to make drastic modifications to PBV structure, from primary to quaternary, in order to promote recognition of target epitopes, potentiate vaccine immunogenicity, and prevent antigen-associated complications. Additionally, these modifications have made it possible to control immune responses by modulating stability and targeting PBV to key immune cells. Consequently, careful consideration should be given to protein structure when designing PBVs in the future in order to potentiate PBV efficacy.

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Section: Pbv Targeting Strategies For Antigenically Variable Pathogensupporting

confidence: 66%

Designs of Antigen Structure and Composition for Improved Protein-Based Vaccine Efficacy

et al. 2020

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“…3 c). A previous study demonstrated that this mutation did not affect replication capacity [ 48 ]. These findings together suggest that the Y135F mutation may impair the suppression of HIV-1 replication by YF9-specific T cells, even though the mutation is not driven by HLA-B*35:01.…”

Section: Resultsmentioning

confidence: 99%

“…NL4-3 mutants (NL4-3YF9-1F) were previously generated by introducing the Nef YF9-1F mutation into NL4-3 using a site-directed mutagenesis system (Invitrogen, USA) [ 48 , 49 ].…”

Section: Methodsmentioning

confidence: 99%

Impact of a single HLA-A24:02-associated escape mutation on the detrimental effect of HLA-B35:01 in HIV-1 control

et al. 2018

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BackgroundHLA-B*35 is an HLA allele associated with rapid progression to AIDS. However, a mechanism underlying the detrimental effect of HLA-B*35 on disease outcome remains unknown. Recent studies demonstrated that most prevalent subtype HLA-B*35:01 is a detrimental allele in HIV-1 clade B-infected individuals. We here investigated the effect of mutations within the epitopes on HLA-B*35:01-restricted CD8+ T cells having abilities to suppress HIV-1 replication.MethodsWe analyzed 16 HLA-B*35:01-restricted epitope-specific T cells in 63 HIV-1 clade B-infected Japanese B*35:01+ individuals and identified HLA-B*35:01-restricted CD8+ T cells having abilities to suppress HIV-1 replication. We further analyzed the effect of HLA-associated mutations on the ability of these T cells.FindingsThe breadth of T cell responses to 4 epitopes was inversely associated with plasma viral load (pVL). However, the accumulation of an Y135F mutation in NefYF9 out of the 4 epitopes, which is selected by HLA-A*24:02-restricted T cells, affected the ability of YF9-specific T cells to suppress HIV-1 replication. HLA-B*35:01+ individuals harboring this mutation had much higher pVL than those without it. YF9-specific T cells failed to suppress replication of the Y135F mutant in vitro. These results indicate that this mutation impairs suppression of HIV-1 replication by YF9-specific T cells.InterpretationThese findings indicate that the Y135F mutation is a key factor underlying the detrimental effect of HLA-B*35:01 on disease outcomes in HIV-1 clade B-infected individuals.FundGrants-in-aid for AIDS Research from AMED and for scientific research from the Ministry of Education, Science, Sports, and Culture, Japan.

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“…Recently, several studies in HIV-1 have found HIV-1-specific CD8 T cells expressed these recombination [37,38], and the crystal structures of TCR-pMHC revealed that TRDV1/TRBV TCR was similar to the TRAV/TRBV structures [39]. Recently, several studies in HIV-1 have found HIV-1-specific CD8 T cells expressed these recombination [37,38], and the crystal structures of TCR-pMHC revealed that TRDV1/TRBV TCR was similar to the TRAV/TRBV structures [39].…”

Section: Discussionmentioning

confidence: 99%

Comparative analysis of CDR3 regions in paired human αβ CD8 T cells

Shi

Lü

et al. 2019

FEBS Open Bio

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The majority of human CD8 cytotoxic T lymphocytes express αβ T‐cell receptors that recognize peptide–MHC class I complexes. Considerable attention has been devoted to TCR β repertoires, but study of TCR α chains has been limited. To gain a better understanding of the features of CDR3α and CDR3β in paired samples, we comprehensively analyzed 776 unique paired αβ TCR CDR3 regions in this study. We found that (I) the CDR3 length among paired αβ TCRs had a fairly narrow distribution due to random assortment of CDR3 length in alpha and beta chains; (II) nucleotide deletions among CDR3 regions were positively correlated with insertions in both α and β TCRs; (III) the CDR3 loops of both α and β chains contained an abundance of charged/polar residues and the CDR3 base regions contained a conserved motif; and (IV) the occurrence of Gly was CDR3 length‐ and position‐dependent in both chains, whereas the frequency of Ser at positions 106 and 107 was positively correlated with CDR3 length in TCR β. Overall, the amino acids in CDR3 loop regions were significantly different between TCR α and β, which suggests a distinct role for each chain in the recognition of antigen–MHC complexes. Here, we have provided detailed information on CDR3 in paired TCRs expressed on human CD8+ T cells and established the basis of a reference set for αβ TCR repertoires in healthy humans.

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Effects of a Single Escape Mutation on T Cell and HIV-1 Co-adaptation

Cited by 20 publications

References 59 publications

Designs of Antigen Structure and Composition for Improved Protein-Based Vaccine Efficacy

Designs of Antigen Structure and Composition for Improved Protein-Based Vaccine Efficacy

Impact of a single HLA-A24:02-associated escape mutation on the detrimental effect of HLA-B35:01 in HIV-1 control

Comparative analysis of CDR3 regions in paired human αβ CD8 T cells

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Effects of a Single Escape Mutation on T Cell and HIV-1 Co-adaptation

Cited by 20 publications

References 59 publications

Designs of Antigen Structure and Composition for Improved Protein-Based Vaccine Efficacy

Designs of Antigen Structure and Composition for Improved Protein-Based Vaccine Efficacy

Impact of a single HLA-A*24:02-associated escape mutation on the detrimental effect of HLA-B*35:01 in HIV-1 control

Comparative analysis of CDR3 regions in paired human αβ CD8 T cells

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Impact of a single HLA-A24:02-associated escape mutation on the detrimental effect of HLA-B35:01 in HIV-1 control