5VUE

HLA-B*57:01 presenting LTVQVARVW

Summary for 5VUE

• Entry DOI: 10.2210/pdb5vue/pdb
• Related: 5VUD 5VUF 5VVP 5VWD 5VWF 5VWH 5VWJ
• Descriptor: HLA class I histocompatibility antigen, B-57 alpha chain, Beta-2-microglobulin, Nonamer peptide: LEU-THR-VAL-GLN-VAL-ALA-ARG-VAL-TRP, ... (4 entities in total)
• Functional Keywords: human leukocyte antigen, antigen presentation, immune system
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 3
• Total formula weight: 44556.61

Authors

Pymm, P.,Rossjohn, J.,Vivian, J.P. (deposition date: 2017-05-19, release date: 2018-10-03, Last modification date: 2023-10-04)

Primary citation

Illing, P.T.,Pymm, P.,Croft, N.P.,Hilton, H.G.,Jojic, V.,Han, A.S.,Mendoza, J.L.,Mifsud, N.A.,Dudek, N.L.,McCluskey, J.,Parham, P.,Rossjohn, J.,Vivian, J.P.,Purcell, A.W.
HLA-B57 micropolymorphism defines the sequence and conformational breadth of the immunopeptidome.
Nat Commun, 9:4693-4693, 2018

PubMed Abstract: Immunophenotypic differences between closely related human leukocyte antigen (HLA) alleles have been associated with divergent clinical outcomes in infection, autoimmunity, transplantation and drug hypersensitivity. Here we explore the impact of micropolymorphism on peptide antigen presentation by three closely related HLA molecules, HLA-B*57:01, HLA-B*57:03 and HLA-B*58:01, that are differentially associated with the HIV elite controller phenotype and adverse drug reactions. For each allotype, we mine HLA ligand data sets derived from the same parental cell proteome to define qualitative differences in peptide presentation using classical peptide binding motifs and an unbiased statistical approach. The peptide repertoires show marked qualitative overlap, with 982 peptides presented by all allomorphs. However, differences in peptide abundance, HLA-peptide stability, and HLA-bound conformation demonstrate that HLA micropolymorphism impacts more than simply the range of peptide ligands. These differences provide grounds for distinct immune reactivity and insights into the capacity of micropolymorphism to diversify immune outcomes.

PubMed: 30410026
DOI: 10.1038/s41467-018-07109-w

Experimental method

X-RAY DIFFRACTION (1.8 Å)