scholarly journals Structural basis for recognition of two HLA-A2-restricted SARS-CoV-2 spike epitopes by public and private T cell receptors

2021 ◽  
Author(s):  
Daichao Wu ◽  
Alexander Kolesnikov ◽  
Rui Yin ◽  
Johnathan Guest ◽  
Ragul Gowthaman ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptors ◽  
Neutralizing Antibodies ◽  
Structural Information ◽  
Vital Role ◽  
Structural Basis ◽  
Long Term Memory ◽  
Public And Private ◽  
Cell Receptors ◽  
Natural Variants

Abstract T cells play a vital role in combatting SARS-CoV-2 and in forming long-term memory responses. Whereas extensive structural information is available on neutralizing antibodies against SARS-CoV-2, such information on SARS-CoV-2-specific T cell receptors (TCRs) bound to their peptide–MHC targets is lacking. We determined structures of a public and a private TCR from COVID-19 convalescent patients in complex with HLA-A2 and two SARS-CoV-2 spike protein epitopes (YLQ and RLQ). The structures revealed the basis for selection of particular TRAV and TRBV germline genes by the public but not the private TCR, and for the ability of both TCRs to recognize natural variants of YLQ and RLQ but not homologous epitopes from human seasonal coronaviruses. By elucidating the mechanism for TCR recognition of an immunodominant yet variable epitope (YLQ) and a conserved but less commonly targeted epitope (RLQ), this study can inform prospective efforts to design vaccines to elicit pan-coronavirus immunity.

scholarly journals Structural basis for recognition of two HLA-A2-restricted SARS-CoV-2 spike epitopes by public and private T cell receptors

2021 ◽  
Author(s):  
Daichao Wu ◽  
Alexander Kolesnikov ◽  
Rui Yin ◽  
Johnathan D Guest ◽  
Ragul Gowthaman ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptors ◽  
Neutralizing Antibodies ◽  
Structural Information ◽  
Vital Role ◽  
Structural Basis ◽  
Long Term Memory ◽  
Public And Private ◽  
Cell Receptors ◽  
Natural Variants

T cells play a vital role in combatting SARS-CoV-2 and in forming long-term memory responses. Whereas extensive structural information is available on neutralizing antibodies against SARS- CoV-2, such information on SARS-CoV-2-specific T cell receptors (TCRs) bound to their peptide-MHC targets is lacking. We determined structures of a public and a private TCR from COVID-19 convalescent patients in complex with HLA-A2 and two SARS-CoV-2 spike protein epitopes (YLQ and RLQ). The structures revealed the basis for selection of particular TRAV and TRBV germline genes by the public but not the private TCR, and for the ability of both TCRs to recognize natural variants of YLQ and RLQ but not homologous epitopes from human seasonal coronaviruses. By elucidating the mechanism for TCR recognition of an immunodominant yet variable epitope (YLQ) and a conserved but less commonly targeted epitope (RLQ), this study can inform prospective efforts to design vaccines to elicit pan-coronavirus immunity.

scholarly journals Structural assessment of HLA-A2-restricted SARS-CoV-2 spike epitopes recognized by public and private T-cell receptors

2022 ◽  
Vol 13 (1) ◽  
Author(s):  
Daichao Wu ◽  
Alexander Kolesnikov ◽  
Rui Yin ◽  
Johnathan D. Guest ◽  
Ragul Gowthaman ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptors ◽  
Neutralizing Antibodies ◽  
Structural Information ◽  
Vital Role ◽  
Long Term Memory ◽  
Public And Private ◽  
Cell Receptors ◽  
Germline Genes ◽  
Natural Variants

AbstractT cells play a vital role in combatting SARS-CoV-2 and forming long-term memory responses. Whereas extensive structural information is available on neutralizing antibodies against SARS-CoV-2, such information on SARS-CoV-2-specific T-cell receptors (TCRs) bound to their peptide–MHC targets is lacking. Here we determine the structures of a public and a private TCR from COVID-19 convalescent patients in complex with HLA-A2 and two SARS-CoV-2 spike protein epitopes (YLQ and RLQ). The structures reveal the basis for selection of particular TRAV and TRBV germline genes by the public but not the private TCR, and for the ability of the TCRs to recognize natural variants of RLQ but not YLQ. Neither TCR recognizes homologous epitopes from human seasonal coronaviruses. By elucidating the mechanism for TCR recognition of an immunodominant yet variable epitope (YLQ) and a conserved but less commonly targeted epitope (RLQ), this study can inform prospective efforts to design vaccines to elicit pan-coronavirus immunity.

scholarly journals The somatically generated portion of T cell receptor CDR3α contributes to the MHC allele specificity of the T cell receptor

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Philippa Marrack ◽  
Sai Harsha Krovi ◽  
Daniel Silberman ◽  
Janice White ◽  
Eleanor Kushnir ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
T Cell ◽  
Positive Selection ◽  
T Cell Receptor ◽  
T Cell Receptors ◽  
Cell Receptor ◽  
Structural Basis ◽  
Major Histocompatibility ◽  
Cell Receptors ◽  
Histocompatibility Complex

Mature T cells bearing αβ T cell receptors react with foreign antigens bound to alleles of major histocompatibility complex proteins (MHC) that they were exposed to during their development in the thymus, a phenomenon known as positive selection. The structural basis for positive selection has long been debated. Here, using mice expressing one of two different T cell receptor β chains and various MHC alleles, we show that positive selection-induced MHC bias of T cell receptors is affected both by the germline encoded elements of the T cell receptor α and β chain and, surprisingly, dramatically affected by the non germ line encoded portions of CDR3 of the T cell receptor α chain. Thus, in addition to determining specificity for antigen, the non germline encoded elements of T cell receptors may help the proteins cope with the extremely polymorphic nature of major histocompatibility complex products within the species.

scholarly journals Structural Basis of Specificity and Cross-Reactivity in T Cell Receptors Specific for Cytochrome c–I-Ek

2011 ◽  
Vol 186 (10) ◽  
pp. 5823-5832 ◽  
Author(s):  
Evan W. Newell ◽  
Lauren K. Ely ◽  
Andrew C. Kruse ◽  
Philip A. Reay ◽  
Stephanie N. Rodriguez ◽  
...  
Keyword(s):  
T Cell ◽  
Cytochrome C ◽  
T Cell Receptors ◽  
Cross Reactivity ◽  
Structural Basis ◽  
Cell Receptors

scholarly journals A Structural Basis for the Selection of Dominant αβ T Cell Receptors in Antiviral Immunity

Immunity ◽  
2003 ◽  
Vol 18 (1) ◽  
pp. 53-64 ◽  
Author(s):  
Lars Kjer-Nielsen ◽  
Craig S. Clements ◽  
Anthony W. Purcell ◽  
Andrew G. Brooks ◽  
James C. Whisstock ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptors ◽  
Antiviral Immunity ◽  
Structural Basis ◽  
Cell Receptors ◽  
Selection Of

Structural basis for self-recognition by autoimmune T-cell receptors

2012 ◽  
Vol 250 (1) ◽  
pp. 32-48 ◽  
Author(s):  
Yiyuan Yin ◽  
Yili Li ◽  
Roy A. Mariuzza
Keyword(s):  
T Cell ◽  
T Cell Receptors ◽  
Structural Basis ◽  
Cell Receptors ◽  
Self Recognition

scholarly journals The somatically generated T cell receptor CDR3α contributes to the MHC allele specificity of the T cell receptor

2017 ◽  
Author(s):  
Philippa Marrack ◽  
Sai Harsha Krovi ◽  
Daniel Silberman ◽  
Janice White ◽  
Eleanora Kushnir ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
T Cell ◽  
Positive Selection ◽  
T Cell Receptor ◽  
T Cell Receptors ◽  
Cell Receptor ◽  
Structural Basis ◽  
Major Histocompatibility ◽  
Cell Receptors ◽  
Histocompatibility Complex

ABSTRACTMature T cells bearing αβ T cell receptors react with foreign antigens bound to alleles of major histocompatibility complex proteins (MHC) that they were exposed to during their development in the thymus, a phenomenon known as positive selection. The structural basis for positive selection has long been debated. Here, using mice expressing one of two different T cell receptor β chains and various MHC alleles, we show that positive selection-induced MHC bias of T cell receptors is affected both by the germline encoded elements of the T cell receptor α and β chain and, surprisingly, dramatically affected by the non germ line encoded CDR3 of the T cell receptor α chain. Thus, in addition to determining specificity for antigen, the non germline encoded elements of T cell receptors may help the proteins cope with the extremely polymorphic nature of major histocompatibility complex products within the species.

scholarly journals T cell receptors for the HIV KK10 epitope from patients with differential immunologic control are functionally indistinguishable

2018 ◽  
Vol 115 (8) ◽  
pp. 1877-1882 ◽  
Author(s):  
Alok V. Joglekar ◽  
Zhe Liu ◽  
Jeffrey K. Weber ◽  
Yong Ouyang ◽  
John D. Jeppson ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Hiv Infection ◽  
Cd8 T Cells ◽  
T Cell Receptors ◽  
Cross Reactivity ◽  
Structural Basis ◽  
Cell Receptors ◽  
Dynamics Simulations

HIV controllers (HCs) are individuals who can naturally control HIV infection, partially due to potent HIV-specific CD8+ T cell responses. Here, we examined the hypothesis that superior function of CD8+ T cells from HCs is encoded by their T cell receptors (TCRs). We compared the functional properties of immunodominant HIV-specific TCRs obtained from HLA-B*2705 HCs and chronic progressors (CPs) following expression in primary T cells. T cells transduced with TCRs from HCs and CPs showed equivalent induction of epitope-specific cytotoxicity, cytokine secretion, and antigen-binding properties. Transduced T cells comparably, albeit modestly, also suppressed HIV infection in vitro and in humanized mice. We also performed extensive molecular dynamics simulations that provided a structural basis for similarities in cytotoxicity and epitope cross-reactivity. These results demonstrate that the differential abilities of HIV-specific CD8+ T cells from HCs and CPs are not genetically encoded in the TCRs alone and must depend on additional factors.

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