Structural Basis for Unusual TCR CDR3β Usage Against an Immunodominant HIV-1 Gag Protein Peptide Restricted to an HLA-B*81:01 Molecule
In HIV infection, some closely associated human leukocyte antigen (HLA) alleles are correlated with distinct clinical outcomes although presenting the same HIV epitopes. The mechanism that underpins this observation is still unknown, but may be due to the essential features of HLA alleles or T cell...
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Frontiers Media S.A.
2022-01-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.822210/full |
| _version_ | 1818715898845855744 |
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| author | Yang Liu Jun Lei Dan San Yi Yang Chonil Paek Zixiong Xia Yongshun Chen Lei Yin |
| author_facet | Yang Liu Jun Lei Dan San Yi Yang Chonil Paek Zixiong Xia Yongshun Chen Lei Yin |
| author_sort | Yang Liu |
| collection | DOAJ |
| description | In HIV infection, some closely associated human leukocyte antigen (HLA) alleles are correlated with distinct clinical outcomes although presenting the same HIV epitopes. The mechanism that underpins this observation is still unknown, but may be due to the essential features of HLA alleles or T cell receptors (TCR). In this study, we investigate how T18A TCR, which is beneficial for a long-term control of HIV in clinic, recognizes immunodominant Gag epitope TL9 (TPQDLTML180-188) from HIV in the context of the antigen presenting molecule HLA-B*81:01. We found that T18A TCR exhibits differential recognition for TL9 restricted by HLA-B*81:01. Furthermore, via structural and biophysical approaches, we observed that TL9 complexes with HLA-B*81:01 undergoes no conformational change after TCR engagement. Remarkably, the CDR3β in T18A complexes does not contact with TL9 at all but with intensive contacts to HLA-B*81:01. The binding kinetic data of T18A TCR revealed that this TCR can recognize TL9 epitope and several mutant versions, which might explain the correlation of T18A TCR with better clinic outcomes despite the relative high mutation rate of HIV. Collectively, we provided a portrait of how CD8+ T cells engage in HIV-mediated T cell response. |
| first_indexed | 2024-12-17T19:10:41Z |
| format | Article |
| id | doaj.art-2d7389b30c27430cbb52cdf5d581727f |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-17T19:10:41Z |
| publishDate | 2022-01-01 |
| publisher | Frontiers Media S.A. |
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| spelling | doaj.art-2d7389b30c27430cbb52cdf5d581727f2022-12-21T21:35:52ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-01-011310.3389/fimmu.2022.822210822210Structural Basis for Unusual TCR CDR3β Usage Against an Immunodominant HIV-1 Gag Protein Peptide Restricted to an HLA-B*81:01 MoleculeYang Liu0Jun Lei1Dan San2Yi Yang3Chonil Paek4Zixiong Xia5Yongshun Chen6Lei Yin7State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, ChinaDepartment of Clinical Oncology, Renmin Hospital of Wuhan University, Wuhan, ChinaState Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, ChinaState Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, ChinaState Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, ChinaState Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, ChinaDepartment of Clinical Oncology, Renmin Hospital of Wuhan University, Wuhan, ChinaState Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, ChinaIn HIV infection, some closely associated human leukocyte antigen (HLA) alleles are correlated with distinct clinical outcomes although presenting the same HIV epitopes. The mechanism that underpins this observation is still unknown, but may be due to the essential features of HLA alleles or T cell receptors (TCR). In this study, we investigate how T18A TCR, which is beneficial for a long-term control of HIV in clinic, recognizes immunodominant Gag epitope TL9 (TPQDLTML180-188) from HIV in the context of the antigen presenting molecule HLA-B*81:01. We found that T18A TCR exhibits differential recognition for TL9 restricted by HLA-B*81:01. Furthermore, via structural and biophysical approaches, we observed that TL9 complexes with HLA-B*81:01 undergoes no conformational change after TCR engagement. Remarkably, the CDR3β in T18A complexes does not contact with TL9 at all but with intensive contacts to HLA-B*81:01. The binding kinetic data of T18A TCR revealed that this TCR can recognize TL9 epitope and several mutant versions, which might explain the correlation of T18A TCR with better clinic outcomes despite the relative high mutation rate of HIV. Collectively, we provided a portrait of how CD8+ T cells engage in HIV-mediated T cell response.https://www.frontiersin.org/articles/10.3389/fimmu.2022.822210/fullHIVT cell receptorCD8+ T cellsHLAantigen presentation |
| spellingShingle | Yang Liu Jun Lei Dan San Yi Yang Chonil Paek Zixiong Xia Yongshun Chen Lei Yin Structural Basis for Unusual TCR CDR3β Usage Against an Immunodominant HIV-1 Gag Protein Peptide Restricted to an HLA-B*81:01 Molecule Frontiers in Immunology HIV T cell receptor CD8+ T cells HLA antigen presentation |
| title | Structural Basis for Unusual TCR CDR3β Usage Against an Immunodominant HIV-1 Gag Protein Peptide Restricted to an HLA-B*81:01 Molecule |
| title_full | Structural Basis for Unusual TCR CDR3β Usage Against an Immunodominant HIV-1 Gag Protein Peptide Restricted to an HLA-B*81:01 Molecule |
| title_fullStr | Structural Basis for Unusual TCR CDR3β Usage Against an Immunodominant HIV-1 Gag Protein Peptide Restricted to an HLA-B*81:01 Molecule |
| title_full_unstemmed | Structural Basis for Unusual TCR CDR3β Usage Against an Immunodominant HIV-1 Gag Protein Peptide Restricted to an HLA-B*81:01 Molecule |
| title_short | Structural Basis for Unusual TCR CDR3β Usage Against an Immunodominant HIV-1 Gag Protein Peptide Restricted to an HLA-B*81:01 Molecule |
| title_sort | structural basis for unusual tcr cdr3β usage against an immunodominant hiv 1 gag protein peptide restricted to an hla b 81 01 molecule |
| topic | HIV T cell receptor CD8+ T cells HLA antigen presentation |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.822210/full |
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