Empty conformers of HLA-B preferentially bind CD8 and regulate CD8+ T cell function
When complexed with antigenic peptides, human leukocyte antigen (HLA) class I (HLA-I) molecules initiate CD8+ T cell responses via interaction with the T cell receptor (TCR) and co-receptor CD8. Peptides are generally critical for the stable cell surface expression of HLA-I molecules. However, for H...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2018-05-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/36341 |
| _version_ | 1818023941550112768 |
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| author | Jie Geng John D Altman Sujatha Krishnakumar Malini Raghavan |
| author_facet | Jie Geng John D Altman Sujatha Krishnakumar Malini Raghavan |
| author_sort | Jie Geng |
| collection | DOAJ |
| description | When complexed with antigenic peptides, human leukocyte antigen (HLA) class I (HLA-I) molecules initiate CD8+ T cell responses via interaction with the T cell receptor (TCR) and co-receptor CD8. Peptides are generally critical for the stable cell surface expression of HLA-I molecules. However, for HLA-I alleles such as HLA-B*35:01, peptide-deficient (empty) heterodimers are thermostable and detectable on the cell surface. Additionally, peptide-deficient HLA-B*35:01 tetramers preferentially bind CD8 and to a majority of blood-derived CD8+ T cells via a CD8-dependent binding mode. Further functional studies reveal that peptide-deficient conformers of HLA-B*35:01 do not directly activate CD8+ T cells, but accumulate at the immunological synapse in antigen-induced responses, and enhance cognate peptide-induced cell adhesion and CD8+ T cell activation. Together, these findings indicate that HLA-I peptide occupancy influences CD8 binding affinity, and reveal a new set of regulators of CD8+ T cell activation, mediated by the binding of empty HLA-I to CD8. |
| first_indexed | 2024-12-10T03:52:19Z |
| format | Article |
| id | doaj.art-4cfd285677144d24a10f9b72ec46393e |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-12-10T03:52:19Z |
| publishDate | 2018-05-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-4cfd285677144d24a10f9b72ec46393e2022-12-22T02:03:13ZengeLife Sciences Publications LtdeLife2050-084X2018-05-01710.7554/eLife.36341Empty conformers of HLA-B preferentially bind CD8 and regulate CD8+ T cell functionJie Geng0https://orcid.org/0000-0001-8722-2228John D Altman1https://orcid.org/0000-0001-9733-2359Sujatha Krishnakumar2https://orcid.org/0000-0003-1961-3432Malini Raghavan3https://orcid.org/0000-0002-1345-9318Department of Microbiology and Immunology, Michigan Medicine, University of Michigan, Ann Arbor, United StatesDepartment of Microbiology and Immunology, Emory University School of Medicine, Atlanta, United States; Yerkes National Primate Research Center, Emory University, Atlanta, United StatesSirona Genomics, Immucor, Inc., California, United StatesDepartment of Microbiology and Immunology, Michigan Medicine, University of Michigan, Ann Arbor, United StatesWhen complexed with antigenic peptides, human leukocyte antigen (HLA) class I (HLA-I) molecules initiate CD8+ T cell responses via interaction with the T cell receptor (TCR) and co-receptor CD8. Peptides are generally critical for the stable cell surface expression of HLA-I molecules. However, for HLA-I alleles such as HLA-B*35:01, peptide-deficient (empty) heterodimers are thermostable and detectable on the cell surface. Additionally, peptide-deficient HLA-B*35:01 tetramers preferentially bind CD8 and to a majority of blood-derived CD8+ T cells via a CD8-dependent binding mode. Further functional studies reveal that peptide-deficient conformers of HLA-B*35:01 do not directly activate CD8+ T cells, but accumulate at the immunological synapse in antigen-induced responses, and enhance cognate peptide-induced cell adhesion and CD8+ T cell activation. Together, these findings indicate that HLA-I peptide occupancy influences CD8 binding affinity, and reveal a new set of regulators of CD8+ T cell activation, mediated by the binding of empty HLA-I to CD8.https://elifesciences.org/articles/36341HLA class ICD8empty HLAimmunological synapseHLA-BHLA-B*35:01 |
| spellingShingle | Jie Geng John D Altman Sujatha Krishnakumar Malini Raghavan Empty conformers of HLA-B preferentially bind CD8 and regulate CD8+ T cell function eLife HLA class I CD8 empty HLA immunological synapse HLA-B HLA-B*35:01 |
| title | Empty conformers of HLA-B preferentially bind CD8 and regulate CD8+ T cell function |
| title_full | Empty conformers of HLA-B preferentially bind CD8 and regulate CD8+ T cell function |
| title_fullStr | Empty conformers of HLA-B preferentially bind CD8 and regulate CD8+ T cell function |
| title_full_unstemmed | Empty conformers of HLA-B preferentially bind CD8 and regulate CD8+ T cell function |
| title_short | Empty conformers of HLA-B preferentially bind CD8 and regulate CD8+ T cell function |
| title_sort | empty conformers of hla b preferentially bind cd8 and regulate cd8 t cell function |
| topic | HLA class I CD8 empty HLA immunological synapse HLA-B HLA-B*35:01 |
| url | https://elifesciences.org/articles/36341 |
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