PMID- 26552660
OWN - NLM
STAT- MEDLINE
DCOM- 20160506
LR  - 20231213
IS  - 1432-1211 (Electronic)
IS  - 0093-7711 (Print)
IS  - 0093-7711 (Linking)
VI  - 68
IP  - 1
DP  - 2016 Jan
TI  - The diversity of the HLA-E-restricted peptide repertoire explains the 
      immunological impact of the Arg107Gly mismatch.
PG  - 29-41
LID - 10.1007/s00251-015-0880-z [doi]
AB  - Human leukocyte antigen (HLA)-E molecules are potent inhibitors of NK 
      cell-mediated killing. Low in polymorphisms, two alleles are widely expressed 
      among diverse populations: HLA-E*01:01 and HLA-E*01:03. Both alleles are 
      distinguished by one SNP resulting in the substitution Arg107Gly. Both alleles 
      present a limited set of peptides derived from class I leader sequences 
      physiologically; however, HLA-E*01:01 presents non-canonical peptides in the 
      absence of HLA class I molecules. To further assess the functional differences 
      between both alleles, we analyzed the peptide repertoire of HLA-E*01:03 by 
      applying soluble HLA technology followed by mass-spectrometric peptide 
      sequencing. HLA-E*01:03 restricted peptides showed a length of 9-17 amino acids 
      and differed in their biophysical properties, no overlap in the peptide 
      repertoire of both allelic variants could be observed; however, both alleles 
      shared marginal peptides from the same proteomic content. Artificial APCs 
      expressing empty HLA-E*01:01 or E*01:03 molecules were generated and stabilized 
      using cognate HLA class I-derived peptide ligands to analyze the impact of 
      residue 107 within the HLA-E heavy chain on the NKG2/CD94 receptor engagement. 
      Differences in peptide stabilization could be translated to the density and 
      half-life time of peptide-HLA-E molecules on the cell surface that subsequently 
      impacted NK cell inhibition as verified by cytotoxicity assays. Taken together, 
      these data illustrate functional differences of HLA-E allelic variants induced by 
      a single amino acid. Furthermore, the function of HLA-E in pathophysiologic 
      situations when the HLA processing machinery is interrupted seems to be more 
      emphasized than previously described, implying a crucial role for HLA-E in tumor 
      or viral immune episodes.
FAU - Celik, Alexander A
AU  - Celik AA
AD  - Institute for Transfusion Medicine, Hannover Medical School, Medical Park, 
      Feodor-Lynen-Str. 5, 30625, Hannover, Germany.
FAU - Kraemer, Thomas
AU  - Kraemer T
AD  - Institute for Transfusion Medicine, Hannover Medical School, Medical Park, 
      Feodor-Lynen-Str. 5, 30625, Hannover, Germany.
FAU - Huyton, Trevor
AU  - Huyton T
AD  - Institute for Transfusion Medicine, Hannover Medical School, Medical Park, 
      Feodor-Lynen-Str. 5, 30625, Hannover, Germany.
FAU - Blasczyk, Rainer
AU  - Blasczyk R
AD  - Institute for Transfusion Medicine, Hannover Medical School, Medical Park, 
      Feodor-Lynen-Str. 5, 30625, Hannover, Germany.
FAU - Bade-Doding, Christina
AU  - Bade-Doding C
AD  - Institute for Transfusion Medicine, Hannover Medical School, Medical Park, 
      Feodor-Lynen-Str. 5, 30625, Hannover, Germany. 
      bade-doeding.christina@mh-hannover.de.
LA  - eng
PT  - Journal Article
DEP - 20151109
PL  - United States
TA  - Immunogenetics
JT  - Immunogenetics
JID - 0420404
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (Membrane Transport Proteins)
RN  - 0 (Peptides)
RN  - 0 (Protein Isoforms)
RN  - 0 (Protein Sorting Signals)
RN  - 0 (tapasin)
RN  - 94ZLA3W45F (Arginine)
RN  - TE7660XO1C (Glycine)
SB  - IM
MH  - Amino Acid Sequence
MH  - Arginine/genetics
MH  - Cell Line
MH  - Cytotoxicity Tests, Immunologic
MH  - Genes, MHC Class I
MH  - Glycine/genetics
MH  - Histocompatibility Antigens Class I/*genetics/*immunology/metabolism
MH  - Humans
MH  - Killer Cells, Natural/immunology
MH  - Lymphocytes/immunology
MH  - Membrane Transport Proteins/metabolism
MH  - Molecular Sequence Data
MH  - Peptides/metabolism
MH  - Polymorphism, Single Nucleotide
MH  - Protein Isoforms
MH  - Protein Sorting Signals/physiology
MH  - HLA-E Antigens
PMC - PMC4701785
OTO - NOTNLM
OT  - Diverse HLA-E peptide repertoire
OT  - HLA-E*01:03
OT  - Non-canonical peptides
OT  - Tumor immune escape
EDAT- 2015/11/11 06:00
MHDA- 2016/05/07 06:00
PMCR- 2015/11/09
CRDT- 2015/11/11 06:00
PHST- 2015/09/18 00:00 [received]
PHST- 2015/10/29 00:00 [accepted]
PHST- 2015/11/11 06:00 [entrez]
PHST- 2015/11/11 06:00 [pubmed]
PHST- 2016/05/07 06:00 [medline]
PHST- 2015/11/09 00:00 [pmc-release]
AID - 10.1007/s00251-015-0880-z [pii]
AID - 880 [pii]
AID - 10.1007/s00251-015-0880-z [doi]
PST - ppublish
SO  - Immunogenetics. 2016 Jan;68(1):29-41. doi: 10.1007/s00251-015-0880-z. Epub 2015 
      Nov 9.