PMID- 28686208
OWN - NLM
STAT- MEDLINE
DCOM- 20180330
LR  - 20230107
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 18
IP  - 7
DP  - 2017 Jul 7
TI  - Structural Elements Recognized by Abacavir-Induced T Cells.
LID - 10.3390/ijms18071464 [doi]
LID - 1464
AB  - Adverse drug reactions are one of the leading causes of morbidity and mortality 
      in health care worldwide. Human leukocyte antigen (HLA) alleles have been 
      strongly associated with drug hypersensitivities, and the causative drugs have 
      been shown to stimulate specific T cells at the sites of autoimmune destruction. 
      The structural elements recognized by drug-specific T cell receptors (TCRs) in 
      vivo are poorly defined. Drug-stimulated T cells express TCRs specific for 
      peptide/HLA complexes, but the characteristics of peptides (sequence, or 
      endogenous or exogenous origin) presented in the context of small molecule drugs 
      are not well studied. Using HLA-B*57:01 mediated hypersensitivity to abacavir as 
      a model system, this study examines structural similarities of HLA presented 
      peptides recognized by drug-specific TCRs. Using the crystal structure of 
      HLA-B*57:01 complexed with abacavir and an immunogenic self peptide, VTTDIQVKV 
      SPT5a 976-984, peptide side chains exhibiting flexibility and solvent exposure 
      were identified as potential drug-specific T cell recognition motifs. Viral 
      sequences with structural motifs similar to the immunogenic self peptide were 
      identified. Abacavir-specific T cell clones were used to determine if virus 
      peptides presented in the context of abacavir stimulate T cell responsiveness. An 
      abacavir-specific T cell clone was stimulated by VTQQAQVRL, corresponding to 
      HSV1/2 230-238, in the context of HLA-B*57:01. These data suggest the T cell 
      polyclonal response to abacavir consists of multiple subsets, including T cells 
      that recognize self peptide/HLA-B*57:01 complexes and crossreact with viral 
      peptide/HLA-B*57:01 complexes due to similarity in TCR contact residues.
FAU - Yerly, Daniel
AU  - Yerly D
AD  - Department of Rheumatology, Immunology and Allergology, University Hospital of 
      Bern, 3010 Bern, Switzerland. daniel.yerly@allergy.unibe.ch.
FAU - Pompeu, Yuri Andreiw
AU  - Pompeu YA
AD  - Harvard Medical School, Cambridge, MA 02138, USA. Yuri_Pompeu@hms.harvard.edu.
FAU - Schutte, Ryan J
AU  - Schutte RJ
AD  - Department of Pathology, Immunology and Laboratory Medicine, University of 
      Florida College of Medicine, Gainesville, FL 32610, USA. rschutte@ufl.edu.
FAU - Eriksson, Klara K
AU  - Eriksson KK
AD  - Department of Rheumatology, Immunology and Allergology, University Hospital of 
      Bern, 3010 Bern, Switzerland. klara.eriksson@allergy.unibe.ch.
FAU - Strhyn, Anette
AU  - Strhyn A
AD  - Department of Microbiology and Immunology, University of Copenhagen, 1165 
      Kobenhavn, Denmark. astryhn@sund.ku.dk.
FAU - Bracey, Austin W
AU  - Bracey AW
AD  - Department of Pathology, Immunology and Laboratory Medicine, University of 
      Florida College of Medicine, Gainesville, FL 32610, USA. bracey.a@ufl.edu.
FAU - Buus, Soren
AU  - Buus S
AD  - Department of Microbiology and Immunology, University of Copenhagen, 1165 
      Kobenhavn, Denmark. sbuus@sund.ku.dk.
FAU - Ostrov, David A
AU  - Ostrov DA
AD  - Department of Pathology, Immunology and Laboratory Medicine, University of 
      Florida College of Medicine, Gainesville, FL 32610, USA. 
      ostroda@pathology.ufl.edu.
LA  - eng
GR  - R01 AI103348/AI/NIAID NIH HHS/United States
PT  - Journal Article
DEP - 20170707
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Dideoxynucleosides)
RN  - 0 (Epitopes)
RN  - 0 (HLA-B Antigens)
RN  - 0 (HLA-B57 antigen)
RN  - 0 (Peptides)
RN  - 0 (Receptors, Antigen, T-Cell)
RN  - WR2TIP26VS (abacavir)
SB  - IM
MH  - Amino Acid Sequence
MH  - Crystallography, X-Ray
MH  - Dideoxynucleosides/*pharmacology
MH  - Epitopes/immunology
MH  - HLA-B Antigens/chemistry/immunology
MH  - Herpes Simplex/immunology
MH  - Humans
MH  - Peptides/chemistry/immunology
MH  - Receptors, Antigen, T-Cell/chemistry/immunology
MH  - T-Lymphocytes/drug effects/*immunology
MH  - Transfection
PMC - PMC5535955
OTO - NOTNLM
OT  - Human Leukocyte Antigen
OT  - crystallography
OT  - drug hypersensitivity
COIS- The authors declare no conflict of interest.
EDAT- 2017/07/08 06:00
MHDA- 2018/03/31 06:00
PMCR- 2017/07/01
CRDT- 2017/07/08 06:00
PHST- 2017/04/27 00:00 [received]
PHST- 2017/06/13 00:00 [revised]
PHST- 2017/06/27 00:00 [accepted]
PHST- 2017/07/08 06:00 [entrez]
PHST- 2017/07/08 06:00 [pubmed]
PHST- 2018/03/31 06:00 [medline]
PHST- 2017/07/01 00:00 [pmc-release]
AID - ijms18071464 [pii]
AID - ijms-18-01464 [pii]
AID - 10.3390/ijms18071464 [doi]
PST - epublish
SO  - Int J Mol Sci. 2017 Jul 7;18(7):1464. doi: 10.3390/ijms18071464.