PMID- 29741477
OWN - NLM
STAT- MEDLINE
DCOM- 20190515
LR  - 20190524
IS  - 2050-084X (Electronic)
IS  - 2050-084X (Linking)
VI  - 7
DP  - 2018 May 9
TI  - Empty conformers of HLA-B preferentially bind CD8 and regulate CD8(+) T cell 
      function.
LID - 10.7554/eLife.36341 [doi]
LID - e36341
AB  - 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.
CI  - (c) 2018, Geng et al.
FAU - Geng, Jie
AU  - Geng J
AUID- ORCID: 0000-0001-8722-2228
AD  - Department of Microbiology and Immunology, Michigan Medicine, University of 
      Michigan, Ann Arbor, United States.
FAU - Altman, John D
AU  - Altman JD
AUID- ORCID: 0000-0001-9733-2359
AD  - Department of Microbiology and Immunology, Emory University School of Medicine, 
      Atlanta, United States.
AD  - Yerkes National Primate Research Center, Emory University, Atlanta, United 
      States.
FAU - Krishnakumar, Sujatha
AU  - Krishnakumar S
AUID- ORCID: 0000-0003-1961-3432
AD  - Sirona Genomics, Immucor, Inc., California, United States.
FAU - Raghavan, Malini
AU  - Raghavan M
AUID- ORCID: 0000-0002-1345-9318
AD  - Department of Microbiology and Immunology, Michigan Medicine, University of 
      Michigan, Ann Arbor, United States.
LA  - eng
GR  - R01 AI044115/AI/NIAID NIH HHS/United States
GR  - R01AI044115/AI/NIAID NIH HHS/United States
GR  - AI044115/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20180509
PL  - England
TA  - Elife
JT  - eLife
JID - 101579614
RN  - 0 (CD8 Antigens)
RN  - 0 (HLA-B protein, human)
RN  - 0 (HLA-B27 Antigen)
SB  - IM
MH  - CD8 Antigens/*metabolism
MH  - CD8-Positive T-Lymphocytes/*immunology
MH  - Cells, Cultured
MH  - HLA-B27 Antigen/*metabolism
MH  - Humans
MH  - Leukocytes, Mononuclear/immunology
MH  - Protein Binding
PMC - PMC5990358
OTO - NOTNLM
OT  - CD8
OT  - HLA class I
OT  - HLA-B
OT  - HLA-B*35:01
OT  - empty HLA
OT  - human
OT  - immunological synapse
OT  - immunology
OT  - inflammation
COIS- JG, JA, MR No competing interests declared, SK is affiliated with the Sirona 
      Genomics, where the HLA genotyping for our study was done. The author has no 
      financial interests to declare
EDAT- 2018/05/10 06:00
MHDA- 2019/05/16 06:00
PMCR- 2018/05/09
CRDT- 2018/05/10 06:00
PHST- 2018/03/02 00:00 [received]
PHST- 2018/04/23 00:00 [accepted]
PHST- 2018/05/10 06:00 [pubmed]
PHST- 2019/05/16 06:00 [medline]
PHST- 2018/05/10 06:00 [entrez]
PHST- 2018/05/09 00:00 [pmc-release]
AID - 36341 [pii]
AID - 10.7554/eLife.36341 [doi]
PST - epublish
SO  - Elife. 2018 May 9;7:e36341. doi: 10.7554/eLife.36341.