PMID- 17559580
OWN - NLM
STAT- MEDLINE
DCOM- 20070926
LR  - 20070611
IS  - 0001-2815 (Print)
IS  - 0001-2815 (Linking)
VI  - 70
IP  - 1
DP  - 2007 Jul
TI  - Extraordinary cross-reactivity of an autoimmune T-cell receptor recognizing 
      specific peptides both on autologous and on allogeneic HLA class II molecules.
PG  - 42-52
AB  - A T-cell receptor's (TCR) recognition of a human leukocyte antigen (HLA)-peptide 
      complex (pHLA) is normally described as being restricted by the HLA molecule and 
      specific for the peptide. This is, however, not always true. Several TCRs have 
      been described, which cross-react with other peptides bound to the restricting 
      HLA molecule. This phenomenon has been considered a variant of molecular mimicry 
      and is suggested to be one of the mechanisms behind autoimmunity. The positive 
      selection of T cells in the thymus imposes low-affinity recognition of the TCRs 
      toward self-pHLA, which increases the probability of the TCR to be promiscuous by 
      nature, and further implies that the T-cell repertoire contains TCRs prone to be 
      autoreactive and thus able to induce autoimmunity. We present an autoimmune TCR 
      showing extreme cross-reactivity to several pHLA comprising both own HLA class II 
      restriction element and allogeneic HLA class II restriction elements in complex 
      with both self-derived and microbially derived peptides. The existence of such a 
      significant cross-reactivity in the context of distinct HLA-DR molecules might be 
      more common among autoimmune TCRs than previously anticipated and potentially 
      reveals a new way of designing altered peptide ligands for therapeutic use.
FAU - Hansen, B E
AU  - Hansen BE
AD  - Department of Clinical Immunology, Rigshospitalet, Copenhagen University 
      Hospital, Blegdamsvej 9, DK-2100 Copenhagen, Denmark. behmail@get2net.dk
FAU - Rasmussen, A H
AU  - Rasmussen AH
FAU - Jakobsen, B K
AU  - Jakobsen BK
FAU - Ryder, L P
AU  - Ryder LP
FAU - Svejgaard, A
AU  - Svejgaard A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Tissue Antigens
JT  - Tissue antigens
JID - 0331072
RN  - 0 (HLA Antigens)
RN  - 0 (Histocompatibility Antigens Class II)
RN  - 0 (Peptides)
RN  - 0 (Receptors, Antigen, T-Cell)
SB  - IM
MH  - Autoimmunity/*immunology
MH  - Cell Line, Transformed
MH  - Cell Transformation, Viral
MH  - Cross Reactions
MH  - HLA Antigens/*immunology/*metabolism
MH  - Herpesvirus 4, Human/physiology
MH  - Histocompatibility Antigens Class II/immunology/metabolism
MH  - Humans
MH  - Hybridomas/immunology
MH  - Molecular Mimicry/genetics/immunology
MH  - Peptides/genetics/*immunology/isolation & purification/*metabolism
MH  - Protein Binding
MH  - Receptors, Antigen, T-Cell/*analysis/genetics/immunology/metabolism
EDAT- 2007/06/15 09:00
MHDA- 2007/09/27 09:00
CRDT- 2007/06/15 09:00
PHST- 2007/06/15 09:00 [pubmed]
PHST- 2007/09/27 09:00 [medline]
PHST- 2007/06/15 09:00 [entrez]
AID - TAN849 [pii]
AID - 10.1111/j.1399-0039.2007.00849.x [doi]
PST - ppublish
SO  - Tissue Antigens. 2007 Jul;70(1):42-52. doi: 10.1111/j.1399-0039.2007.00849.x.