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http://purl.uniprot.org/citations/34523962http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/34523962http://www.w3.org/2000/01/rdf-schema#comment"Although mutant-specific T cells are elicited in some individuals infected with HIV-1 mutant viruses, the detailed characteristics of these T cells remain unknown. A recent study showed that the accumulation of strains expressing Nef135F, which were selected by HLA-A*24:02-restricted T cells, was associated with poor outcomes in individuals with the detrimental HLA-B*35:01 allele and that HLA-B*35:01-restricted NefYF9 (Nef135-143)-specific T cells failed to recognize target cells infected with Nef135F mutant viruses. Here, we investigated HLA-B*35:01-restricted T cells specific for the NefFF9 epitope incorporating the Nef135F mutation. Longitudinal T-cell receptor (TCR) clonotype analysis demonstrated that 3 types of HLA-B*35:01-restricted T cells (wild-type [WT] specific, mutant specific, and cross-reactive) with different T cell repertoires were elicited during the clinical course. HLA-B*35:01+ individuals possessing wild-type-specific T cells had a significantly lower plasma viral load (pVL) than those with mutant-specific and/or cross-reactive T cells, even though the latter T cells effectively recognized the mutant virus-infected cells. These results suggest that mutant-specific and cross-reactive T cells could only partially suppress HIV-1 replication in vivo. An ex vivo analysis of the T cells showed higher expression of PD-1 on cross-reactive T cells and lower expression of CD160/2B4 on the mutant-specific T cells than other T cells, implying that these inhibitory and stimulatory molecules are key to the reduced function of these T cells. In the present study, we demonstrate that mutant-specific and cross-reactive T cells do not contribute to the suppression of HIV-1 replication in HIV-1-infected individuals, even though they have the capacity to recognize mutant virus-infected cells. Thus, the collaboration of HLA-A*24:02 with the detrimental allele HLA-B*35:01 resulted in the coevolution of HIV-1 alongside virus-specific T cells, leading to poorer clinical outcomes. IMPORTANCE HIV-1 escape mutations are selected under pressure from HIV-1-specific CD8+ T cells. Accumulation of these mutations in circulating viruses impairs the control of HIV-1 by HIV-1-specific T cells. Although it is known that HIV-1-specific T cells recognizing mutant virus were elicited in some individuals infected with a mutant virus, the role of these T cells remains unclear. Accumulation of phenylalanine at HIV-1 Nef135 (Nef135F), which is selected by HLA-A*24:02-restricted T cells, led to poor clinical outcome in individuals carrying the detrimental HLA-B*35:01 allele. In the present study, we found that HLA-B*35:01-restricted mutant-specific and cross-reactive T cells were elicited in HLA-B*35:01+ individuals infected with the Nef135F mutant virus. These T cells could not effectively suppress HIV-1 replication in vivo even though they could recognize mutant virus-infected cells in vitro. Mutant-specific and cross-reactive T cells expressed lower levels of stimulatory molecules and higher levels of inhibitory molecules, respectively, suggesting a potential mechanism whereby these T cells fail to suppress HIV-1 replication in HIV-1-infected individuals."xsd:string
http://purl.uniprot.org/citations/34523962http://purl.org/dc/terms/identifier"doi:10.1128/jvi.01259-21"xsd:string
http://purl.uniprot.org/citations/34523962http://purl.uniprot.org/core/author"Oka S."xsd:string
http://purl.uniprot.org/citations/34523962http://purl.uniprot.org/core/author"Takiguchi M."xsd:string
http://purl.uniprot.org/citations/34523962http://purl.uniprot.org/core/author"Murakoshi H."xsd:string
http://purl.uniprot.org/citations/34523962http://purl.uniprot.org/core/author"Gatanaga H."xsd:string
http://purl.uniprot.org/citations/34523962http://purl.uniprot.org/core/author"Kuse N."xsd:string
http://purl.uniprot.org/citations/34523962http://purl.uniprot.org/core/author"Rowland-Jones S.L."xsd:string
http://purl.uniprot.org/citations/34523962http://purl.uniprot.org/core/author"Akahoshi T."xsd:string
http://purl.uniprot.org/citations/34523962http://purl.uniprot.org/core/author"Chikata T."xsd:string
http://purl.uniprot.org/citations/34523962http://purl.uniprot.org/core/author"James K.L."xsd:string
http://purl.uniprot.org/citations/34523962http://purl.uniprot.org/core/date"2021"xsd:gYear
http://purl.uniprot.org/citations/34523962http://purl.uniprot.org/core/name"J Virol"xsd:string
http://purl.uniprot.org/citations/34523962http://purl.uniprot.org/core/pages"e0125921"xsd:string
http://purl.uniprot.org/citations/34523962http://purl.uniprot.org/core/title"Collaboration of a Detrimental HLA-B*35:01 Allele with HLA-A*24:02 in Coevolution of HIV-1 with T Cells Leading to Poorer Clinical Outcomes."xsd:string
http://purl.uniprot.org/citations/34523962http://purl.uniprot.org/core/volume"95"xsd:string
http://purl.uniprot.org/citations/34523962http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/34523962
http://purl.uniprot.org/citations/34523962http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/34523962
http://purl.uniprot.org/uniprot/#_A0A0A7C543-mappedCitation-34523962http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/34523962
http://purl.uniprot.org/uniprot/#_A0A0A7C548-mappedCitation-34523962http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/34523962
http://purl.uniprot.org/uniprot/#_A0A0A7C551-mappedCitation-34523962http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/34523962
http://purl.uniprot.org/uniprot/#_A0A0A7C552-mappedCitation-34523962http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/34523962
http://purl.uniprot.org/uniprot/#_A0A0E3DC98-mappedCitation-34523962http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/34523962
http://purl.uniprot.org/uniprot/#_A0A0E3DCA0-mappedCitation-34523962http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/34523962
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