PMID- 19617574
OWN - NLM
STAT- MEDLINE
DCOM- 20090929
LR  - 20210206
IS  - 1528-0020 (Electronic)
IS  - 0006-4971 (Linking)
VI  - 114
IP  - 11
DP  - 2009 Sep 10
TI  - Cross-recognition of HLA DR4 alloantigen by virus-specific CD8+ T cells: a new 
      paradigm for self-/nonself-recognition.
PG  - 2244-53
LID - 10.1182/blood-2009-05-222596 [doi]
AB  - The ability of CD8(+) T cells to engage a diverse range of peptide-major 
      histocompatibility complex (MHC) complexes can also lead to cross-recognition of 
      self and nonself peptide-MHC complexes and thus directly contribute toward 
      allograft rejection or autoimmunity. Here we present a novel form of 
      cross-recognition by herpes virus-specific CD8(+) cytotoxic T cells that 
      challenges the current paradigm of self/non-self recognition. Functional 
      characterization of a human leukocyte antigen (HLA) Cw*0602-restricted 
      cytomegalovirus-specific CD8(+) T-cell response revealed an unusual dual 
      specificity toward a pp65 epitope and the alloantigen HLA DR4. This 
      cross-recognition of HLA DR4 alloantigen was critically dependent on the 
      coexpression of HLA DM and was preferentially directed toward the B-cell lineage. 
      Furthermore, allostimulation of peripheral blood lymphocytes with HLA 
      DRB*0401-expressing cells rapidly expanded CD8(+) T cells, which recognized the 
      pp65 epitope in the context of HLA Cw*0602. T-cell repertoire analysis revealed 2 
      dominant populations expressing T-cell receptor beta variable (TRBV)4-3 or 
      TRBV13, with cross-reactivity exclusively mediated by the TRBV13(+) clonotypes. 
      More importantly, cross-reactive TRBV13(+) clonotypes displayed markedly lower 
      T-cell receptor binding affinity and a distinct pattern of peptide recognition, 
      presumably mimicking a structure presented on the HLA DR4 allotype. These results 
      illustrate a novel mechanism whereby virus-specific CD8(+) T cells can 
      cross-recognize HLA class II molecules and may contribute toward allograft 
      rejection and/or autoimmunity.
FAU - Rist, Michael
AU  - Rist M
AD  - Australian Centre for Vaccine Development and Tumour Immunology Laboratory, 
      Division of Infectious Immunology, Queensland Institute of Medical Research, 
      Brisbane, Australia.
FAU - Smith, Corey
AU  - Smith C
FAU - Bell, Melissa J
AU  - Bell MJ
FAU - Burrows, Scott R
AU  - Burrows SR
FAU - Khanna, Rajiv
AU  - Khanna R
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090717
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Epitopes, T-Lymphocyte)
RN  - 0 (HLA-C Antigens)
RN  - 0 (HLA-DR4 Antigen)
RN  - 0 (Peptides)
RN  - 0 (Phosphoproteins)
RN  - 0 (Receptors, Antigen, T-Cell, alpha-beta)
RN  - 0 (Viral Matrix Proteins)
RN  - 0 (cytomegalovirus matrix protein 65kDa)
SB  - IM
MH  - Autoimmunity/*immunology
MH  - CD8-Positive T-Lymphocytes/*immunology
MH  - Cell Line, Transformed
MH  - Cytomegalovirus/*immunology
MH  - Epitopes, T-Lymphocyte/immunology
MH  - Graft Rejection/*immunology
MH  - HLA-C Antigens/immunology
MH  - HLA-DR4 Antigen/*immunology
MH  - Humans
MH  - Peptides/*immunology
MH  - Phosphoproteins/*immunology
MH  - Receptors, Antigen, T-Cell, alpha-beta/immunology
MH  - Transplantation, Homologous
MH  - Viral Matrix Proteins/*immunology
EDAT- 2009/07/21 09:00
MHDA- 2009/09/30 06:00
CRDT- 2009/07/21 09:00
PHST- 2009/07/21 09:00 [entrez]
PHST- 2009/07/21 09:00 [pubmed]
PHST- 2009/09/30 06:00 [medline]
AID - S0006-4971(20)36940-8 [pii]
AID - 10.1182/blood-2009-05-222596 [doi]
PST - ppublish
SO  - Blood. 2009 Sep 10;114(11):2244-53. doi: 10.1182/blood-2009-05-222596. Epub 2009 
      Jul 17.