PMID- 22227099
OWN - NLM
STAT- MEDLINE
DCOM- 20120611
LR  - 20120220
IS  - 1879-1166 (Electronic)
IS  - 0198-8859 (Linking)
VI  - 73
IP  - 3
DP  - 2012 Mar
TI  - Structural aspects of human leukocyte antigen class I epitopes detected by human 
      monoclonal antibodies.
PG  - 267-77
LID - 10.1016/j.humimm.2011.11.011 [doi]
AB  - This study addresses the concept that human leukocyte antigen (HLA) class 
      I-specific alloantibodies are specific for epitopes that correspond to 
      HLAMatchmaker-defined eplets. Eplets are essential parts of so-called structural 
      epitopes that make contact with the 6 complementarity determining regions of an 
      antibody. From published molecular models of crystallized protein 
      antigen-antibody complexes, we have calculated that contact residues on 
      structural HLA epitopes should reside within a 15-A radius of a mismatched eplet. 
      This study addresses the structural basis of high-frequency HLA class I epitopes 
      reacting with human monoclonal antibodies (mAbs) derived from women sensitized 
      during pregnancy. All mAbs were tested in Luminex assays with single HLA allele 
      panels. The HLAMatchmaker algorithm was used to determine their specificity in 
      context with eplet sharing between the immunizing allele and antibody-reactive 
      alleles. To assess the autoreactive B cell origin of these antibodies, we have 
      applied the recently developed nonself-self paradigm of epitope immunogenicity to 
      analyze residue differences between the immunizer and the alleles of the antibody 
      producer. A total of 9 mAbs were specific for epitopes associated with the 41T, 
      80NRG, 163LW, 69AA, or 80ERILR eplets. In each case, the immunizing allele had 
      within 15 A of the mismatched eplet, no residue differences with 1 of the alleles 
      of the antibody producer. This observation is consistent with the concept that 
      these mAbs originated from B cells with self HLA immunoglobulin receptors. 
      Eplet-carrying alleles exhibited different levels of reactivity, which, when 
      compared with the immunizing allele, ranged from high to intermediate to very 
      low. In many cases, lower reactivities were associated with differences from self 
      to nonself residues in surface locations within 15 A of the specific eplet. 
      Apparently, such locations may serve as critical contact sites for the antibody. 
      In other cases, other residue differences did not appear to affect binding with 
      the antibody, suggesting that these locations do not play a major role in 
      antibody binding. For these mAbs we did not obtain convincing evidence that 
      residue differences in hidden positions below the molecular surface had 
      significant effects on antibody binding. These findings have increased our 
      understanding of the structural basis of the immunogenicity and antigenicity of 
      HLA class I epitopes and provide a basis for interpreting HLA antibody reactivity 
      patterns in Luminex assays with single alleles.
CI  - Copyright A(c) 2012 American Society for Histocompatibility and Immunogenetics. 
      Published by Elsevier Inc. All rights reserved.
FAU - Duquesnoy, Rene J
AU  - Duquesnoy RJ
AD  - Division of Transplantation Pathology, University of Pittsburgh Medical Center, 
      Pittsburgh, PA 15261, USA. Duquesnoyr@upmc.edu
FAU - Marrari, Marilyn
AU  - Marrari M
FAU - Mulder, Arend
AU  - Mulder A
FAU - Claas, Frans H J
AU  - Claas FH
FAU - Mostecki, Justin
AU  - Mostecki J
FAU - Balazs, Ivan
AU  - Balazs I
LA  - eng
PT  - Journal Article
DEP - 20111208
PL  - United States
TA  - Hum Immunol
JT  - Human immunology
JID - 8010936
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Autoantigens)
RN  - 0 (Epitopes, B-Lymphocyte)
RN  - 0 (HLA Antigens)
SB  - IM
MH  - Algorithms
MH  - Antibodies, Monoclonal/immunology
MH  - Antigen-Antibody Reactions/immunology
MH  - Autoantigens/*chemistry/immunology
MH  - Computational Biology
MH  - Crystallization
MH  - Epitopes, B-Lymphocyte/*chemistry/immunology
MH  - Female
MH  - HLA Antigens/*chemistry/immunology
MH  - Humans
MH  - Hybridomas
MH  - Immunization
MH  - Models, Chemical
MH  - Pregnancy
MH  - Protein Binding
MH  - Protein Conformation
MH  - Software
EDAT- 2012/01/10 06:00
MHDA- 2012/06/12 06:00
CRDT- 2012/01/10 06:00
PHST- 2011/10/05 00:00 [received]
PHST- 2011/11/08 00:00 [revised]
PHST- 2011/11/30 00:00 [accepted]
PHST- 2012/01/10 06:00 [entrez]
PHST- 2012/01/10 06:00 [pubmed]
PHST- 2012/06/12 06:00 [medline]
AID - S0198-8859(11)00584-2 [pii]
AID - 10.1016/j.humimm.2011.11.011 [doi]
PST - ppublish
SO  - Hum Immunol. 2012 Mar;73(3):267-77. doi: 10.1016/j.humimm.2011.11.011. Epub 2011 
      Dec 8.