4JQX

HLA-B*44:03 in complex with Epstein-Barr virus BZLF1-derived peptide (residues 169-180)

Summary for 4JQX

• Entry DOI: 10.2210/pdb4jqx/pdb
• Related: 4JQV
• Descriptor: HLA class I histocompatibility antigen, B-44 alpha chain, Beta-2-microglobulin, Trans-activator protein BZLF1, ... (6 entities in total)
• Functional Keywords: immunoglobulin fold, antigen presentation, t-cell receptor, extracellular, immune system
• Biological source: Homo sapiens (human); More
• Cellular location: Membrane; Single-pass type I membrane protein: P30481; Host nucleus (By similarity): P61769; Secreted: Q3KSS8
• Total number of polymer chains: 3
• Total formula weight: 45626.47

Authors

Theodossis, A.,Welland, A.,Gras, S.,Rossjohn, J. (deposition date: 2013-03-20, release date: 2013-06-26, Last modification date: 2023-09-20)

Primary citation

Rist, M.J.,Theodossis, A.,Croft, N.P.,Neller, M.A.,Welland, A.,Chen, Z.,Sullivan, L.C.,Burrows, J.M.,Miles, J.J.,Brennan, R.M.,Gras, S.,Khanna, R.,Brooks, A.G.,McCluskey, J.,Purcell, A.W.,Rossjohn, J.,Burrows, S.R.
HLA Peptide Length Preferences Control CD8+ T Cell Responses.
J.Immunol., 191:561-571, 2013

PubMed Abstract: Class I HLAs generally present peptides of 8-10 aa in length, although it is unclear whether peptide length preferences are affected by HLA polymorphism. In this study, we investigated the CD8(+) T cell response to the BZLF1 Ag of EBV, which includes overlapping sequences of different size that nevertheless conform to the binding motif of the large and abundant HLA-B*44 supertype. Whereas HLA-B*18:01(+) individuals responded strongly and exclusively to the octamer peptide (173)SELEIKRY(180), HLA-B*44:03(+) individuals responded to the atypically large dodecamer peptide (169)EECDSELEIKRY(180), which encompasses the octamer peptide. Moreover, the octamer peptide bound more stably to HLA-B*18:01 than did the dodecamer peptide, whereas, conversely, HLA-B*44:03 bound only the longer peptide. Furthermore, crystal structures of these viral peptide-HLA complexes showed that the Ag-binding cleft of HLA-B*18:01 was more ideally suited to bind shorter peptides, whereas HLA-B*44:03 exhibited characteristics that favored the presentation of longer peptides. Mass spectrometric identification of > 1000 naturally presented ligands revealed that HLA-B*18:01 was more biased toward presenting shorter peptides than was HLA-B*44:03. Collectively, these data highlight a mechanism through which polymorphism within an HLA class I supertype can diversify determinant selection and immune responses by varying peptide length preferences.

PubMed: 23749632
DOI: 10.4049/jimmunol.1300292

Experimental method

X-RAY DIFFRACTION (1.9 Å)