PMID- 9920851
OWN - NLM
STAT- MEDLINE
DCOM- 19990218
LR  - 20210216
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 93
IP  - 3
DP  - 1999 Feb 1
TI  - Direct alloreactivity by human cytotoxic T lymphocytes can Be inhibited by 
      altered peptide ligand antagonism.
PG  - 1020-4
AB  - Alloreactive T lymphocytes that respond directly to foreign major 
      histocompatibility complex (MHC) molecules and bound peptide are known to be 
      central mediators of graft-versus-host disease (GVHD) and allograft rejection. We 
      have recently identified a peptide from the human protein, cytochrome P450 
      (isotypes IIC9, 10, or 18), that is recognized in association with human 
      leukocyte antigen (HLA) B*3501 by alloreactive cytotoxic T lymphocytes (CTLs). 
      These CTLs with this specificity were isolated from several unrelated individuals 
      and were found to express a common T-cell receptor (TCR). Synthetic analogs of 
      the cytochrome P450 peptide were generated by introducing single amino acid 
      substitutions at putative TCR contact positions. Four altered peptide ligands 
      were powerful competitive antagonists of these CTL clones, reducing lysis levels 
      of target cells expressing the alloantigen HLA B*3501 by over 80%. This first 
      demonstration that it is possible to suppress CTL alloreactivity with structural 
      variants of allodeterminants raises the prospect that such TCR antagonists could 
      be exploited within the clinical arena to specifically modulate GVHD and 
      allograft rejection.
FAU - Burrows, S R
AU  - Burrows SR
AD  - Queensland Institute of Medical Research and University of Queensland Joint 
      Oncology Program, Brisbane, Australia. scottB@qimr.edu.au
FAU - Khanna, R
AU  - Khanna R
FAU - Moss, D J
AU  - Moss DJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (HLA-B Antigens)
RN  - 0 (Ligands)
RN  - 0 (Peptide Fragments)
RN  - 0 (Receptors, Antigen, T-Cell)
RN  - 9035-51-2 (Cytochrome P-450 Enzyme System)
SB  - IM
MH  - Amino Acid Substitution
MH  - Cytochrome P-450 Enzyme System/chemistry/*immunology/metabolism
MH  - Cytotoxicity, Immunologic/drug effects
MH  - Graft vs Host Disease/*immunology
MH  - HLA-B Antigens/*immunology
MH  - Humans
MH  - Ligands
MH  - Peptide Fragments/metabolism/*pharmacology
MH  - Receptors, Antigen, T-Cell/immunology/metabolism
MH  - T-Lymphocytes, Cytotoxic/*drug effects/immunology
EDAT- 1999/01/28 00:00
MHDA- 1999/01/28 00:01
CRDT- 1999/01/28 00:00
PHST- 1999/01/28 00:00 [pubmed]
PHST- 1999/01/28 00:01 [medline]
PHST- 1999/01/28 00:00 [entrez]
AID - S0006-4971(20)48817-2 [pii]
PST - ppublish
SO  - Blood. 1999 Feb 1;93(3):1020-4.