PMID- 21063243
OWN - NLM
STAT- MEDLINE
DCOM- 20110128
LR  - 20101216
IS  - 1534-6080 (Electronic)
IS  - 0041-1337 (Linking)
VI  - 90
IP  - 12
DP  - 2010 Dec 27
TI  - Human monoclonal antibody reactivity with human leukocyte antigen class I 
      epitopes defined by pairs of mismatched eplets and self-eplets.
PG  - 1468-72
LID - 10.1097/TP.0b013e3182007b74 [doi]
AB  - AIM: Humoral sensitization affects transplant outcome, and it is now apparent 
      that human leukocyte antigen (HLA) antibodies are specific for epitopes rather 
      than antigens. Such epitopes can be structurally defined by HLAMatchmaker, an 
      algorithm that considers eplets as critical elements of epitopes recognized by 
      alloantibodies. This study addressed the question how mismatched HLA antigens 
      induce specific antibodies in context with eplet differences with the antibody 
      producer. METHODS: HLA class I-specific human monoclonal antibodies derived from 
      women sensitized during pregnancy were tested in Luminex assays with single 
      allele panels. Their epitope specificity was determined from reactivity patterns 
      and eplet differences between immunizing antigen and the antibody producer. 
      RESULTS: This study focuses on the reactivity patterns of 10 monoclonal 
      antibodies specific for epitopes defined by a mismatched eplet paired with a 
      self-eplet shared between immunizing HLA antigens and HLA antigens of the 
      antibody producer. The eplets in these pairs are between 7 and 16 A apart, a 
      sufficient distance for contact by two separate complementarity-determining 
      regions of antibody. CONCLUSIONS: These findings demonstrate that immunizing 
      antigens have mismatched eplets that can form antibody-reactive epitopes with 
      self-configurations on the molecular surface. They seem to suggest that HLA 
      antibodies can be produced by autoreactive B cells that have undergone receptor 
      editing to accommodate the recognition of nonself-eplets, the driving force of 
      the humoral alloresponse. This concept enhances our understanding of structural 
      epitope immunogenicity and the interpretation of antibody reactivity patterns 
      with HLA panels.
FAU - Marrari, Marilyn
AU  - Marrari M
AD  - Division of Transplantation Pathology, University of Pittsburgh Medical Center, 
      Pittsburgh, PA, USA.
FAU - Mostecki, Justin
AU  - Mostecki J
FAU - Mulder, Arend
AU  - Mulder A
FAU - Claas, Frans
AU  - Claas F
FAU - Balazs, Ivan
AU  - Balazs I
FAU - Duquesnoy, Rene J
AU  - Duquesnoy RJ
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Transplantation
JT  - Transplantation
JID - 0132144
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Autoantibodies)
RN  - 0 (Epitopes)
RN  - 0 (HLA Antigens)
RN  - 0 (Histocompatibility Antigens Class I)
SB  - IM
MH  - Algorithms
MH  - Antibodies, Monoclonal/chemistry/immunology
MH  - Antibody Specificity
MH  - Autoantibodies/immunology
MH  - Epitopes/immunology
MH  - Female
MH  - Graft Rejection/*immunology
MH  - HLA Antigens/immunology
MH  - Histocompatibility Antigens Class I/chemistry/*immunology
MH  - Histocompatibility Testing/methods
MH  - Humans
MH  - Immunity, Humoral
MH  - Models, Molecular
MH  - Pregnancy
MH  - Transplantation Immunology
EDAT- 2010/11/11 06:00
MHDA- 2011/02/01 06:00
CRDT- 2010/11/11 06:00
PHST- 2010/11/11 06:00 [entrez]
PHST- 2010/11/11 06:00 [pubmed]
PHST- 2011/02/01 06:00 [medline]
AID - 10.1097/TP.0b013e3182007b74 [doi]
PST - ppublish
SO  - Transplantation. 2010 Dec 27;90(12):1468-72. doi: 10.1097/TP.0b013e3182007b74.