Crystal structure of the complex between CD8αα human and HLA-A2
The dimeric cell-surface glycoprotein CD8 is crucial to the positive selection of cytotoxic T cells in the thymus. The homodimer CD8αα or the heterodimer αβ stabilizes the interaction of the T-cell antigen receptor (TCR) with major histocompatibility complex (MHC) class l/peptide by binding to the c...
| Main Authors: | , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
1997
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| _version_ | 1826275512924766208 |
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| author | Gao, G Tormo, J Gerth, U Wyer, JR Mcmichael, A Stuart, D Bell, J Jones, E Jakobsen, B |
| author_facet | Gao, G Tormo, J Gerth, U Wyer, JR Mcmichael, A Stuart, D Bell, J Jones, E Jakobsen, B |
| author_sort | Gao, G |
| collection | OXFORD |
| description | The dimeric cell-surface glycoprotein CD8 is crucial to the positive selection of cytotoxic T cells in the thymus. The homodimer CD8αα or the heterodimer αβ stabilizes the interaction of the T-cell antigen receptor (TCR) with major histocompatibility complex (MHC) class l/peptide by binding to the class I molecule. Here we report the crystal structure at 2.7 Å resolution of a complex between CD8αα and the human MHC molecule HLA-A2, which is associated with peptide. CD8αα binds one HLA-A2/peptide molecule, interfacing with the α2 and α3 domains of HLA-A2 and also contacting β2- microglobulin. A flexible loop of the α3 domain (residues 223-229) is damped between the complementarity-determining region (CDR)-like loops of the two CD8 subunits in the classic manner of an antibody-antigen interaction, precluding the binding of a second MHC molecule. The position of the α3 domain is different from that in uncomplexed HLA-A2 (refs 3, 4), being most similar to that in the TCR/Tax/HLA-A2 complex, but no conformational change extends to the MHC/peptide surface presented for TCR recognition. Although these shifts in α3 may provide a synergistic modulation of affinity, the binding of CD8 to MHC is dearly consistent with an avidity-based contribution from CD8 to TCR-peptide-MHC interactions. |
| first_indexed | 2024-03-06T22:59:51Z |
| format | Journal article |
| id | oxford-uuid:61b8baf0-5e88-4153-80be-be919d80965c |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T22:59:51Z |
| publishDate | 1997 |
| record_format | dspace |
| spelling | oxford-uuid:61b8baf0-5e88-4153-80be-be919d80965c2022-03-26T18:01:58ZCrystal structure of the complex between CD8αα human and HLA-A2Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:61b8baf0-5e88-4153-80be-be919d80965cEnglishSymplectic Elements at Oxford1997Gao, GTormo, JGerth, UWyer, JRMcmichael, AStuart, DBell, JJones, EJakobsen, BThe dimeric cell-surface glycoprotein CD8 is crucial to the positive selection of cytotoxic T cells in the thymus. The homodimer CD8αα or the heterodimer αβ stabilizes the interaction of the T-cell antigen receptor (TCR) with major histocompatibility complex (MHC) class l/peptide by binding to the class I molecule. Here we report the crystal structure at 2.7 Å resolution of a complex between CD8αα and the human MHC molecule HLA-A2, which is associated with peptide. CD8αα binds one HLA-A2/peptide molecule, interfacing with the α2 and α3 domains of HLA-A2 and also contacting β2- microglobulin. A flexible loop of the α3 domain (residues 223-229) is damped between the complementarity-determining region (CDR)-like loops of the two CD8 subunits in the classic manner of an antibody-antigen interaction, precluding the binding of a second MHC molecule. The position of the α3 domain is different from that in uncomplexed HLA-A2 (refs 3, 4), being most similar to that in the TCR/Tax/HLA-A2 complex, but no conformational change extends to the MHC/peptide surface presented for TCR recognition. Although these shifts in α3 may provide a synergistic modulation of affinity, the binding of CD8 to MHC is dearly consistent with an avidity-based contribution from CD8 to TCR-peptide-MHC interactions. |
| spellingShingle | Gao, G Tormo, J Gerth, U Wyer, JR Mcmichael, A Stuart, D Bell, J Jones, E Jakobsen, B Crystal structure of the complex between CD8αα human and HLA-A2 |
| title | Crystal structure of the complex between CD8αα human and HLA-A2 |
| title_full | Crystal structure of the complex between CD8αα human and HLA-A2 |
| title_fullStr | Crystal structure of the complex between CD8αα human and HLA-A2 |
| title_full_unstemmed | Crystal structure of the complex between CD8αα human and HLA-A2 |
| title_short | Crystal structure of the complex between CD8αα human and HLA-A2 |
| title_sort | crystal structure of the complex between cd8αα human and hla a2 |
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