PMID- 14630515
OWN - NLM
STAT- MEDLINE
DCOM- 20040309
LR  - 20181113
IS  - 0091-6765 (Print)
IS  - 0091-6765 (Linking)
VI  - 111
IP  - 15
DP  - 2003 Nov
TI  - Electrostatic potential on human leukocyte antigen: implications for putative 
      mechanism of chronic beryllium disease.
PG  - 1827-34
AB  - The pathobiology of chronic beryllium disease (CBD) involves the major 
      histocompatibility complex class II human leukocyte antigen (HLA). Although 
      occupational exposure to beryllium is the cause of CBD, molecular epidemiologic 
      studies suggest that specific (Italic)HLA-DPB1(/Italic) alleles may be genetic 
      susceptibility factors. We have studied three-dimensional structural models of 
      HLA-DP proteins encoded by these genes. The extracellular domains of 
      HLA-DPA1*0103/B1*1701, *1901, *0201, and *0401, and HLA-DPA1*0201/B1*1701, *1901, 
      *0201, and *0401 were modeled from the X-ray coordinates of an HLA-DR template. 
      Using these models, the electrostatic potential at the molecular surface of each 
      HLA-DP was calculated and compared. These comparisons identify specific 
      characteristics in the vicinity of the antigen-binding pocket that distinguish 
      the different HLA-DP allotypes. Differences in electrostatics originate from the 
      shape, specific disposition, and variation in the negatively charged groups 
      around the pocket. The more negative the pocket potential, the greater the odds 
      of developing CBD estimated from reported epidemiologic studies. Adverse impact 
      is caused by charged substitutions in positions 55, 56, 69, 84, and 85, namely, 
      the exact same loci identified as genetic markers of CBD susceptibility as well 
      as cobalt-lung hard metal disease. These findings suggest that certain 
      substitutions may promote an involuntary cation-binding site within a putatively 
      metal-free peptide-binding pocket and therefore change the innate specificity of 
      antigen recognition.
FAU - Snyder, James A
AU  - Snyder JA
AD  - Health Effects Laboratory Division, National Institute for Occupational Safety 
      and Health, Centers for Disease Control and Prevention, 1095 Willowdale Road, 
      Morgantown, WV 26505, USA.
FAU - Weston, Ainsley
AU  - Weston A
FAU - Tinkle, Sally S
AU  - Tinkle SS
FAU - Demchuk, Eugene
AU  - Demchuk E
LA  - eng
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PT  - Review
PL  - United States
TA  - Environ Health Perspect
JT  - Environmental health perspectives
JID - 0330411
RN  - 0 (Cations)
RN  - 0 (HLA-DP Antigens)
SB  - IM
MH  - Amino Acid Sequence
MH  - Berylliosis/immunology/*physiopathology
MH  - Cations
MH  - Chronic Disease
MH  - *Genetic Predisposition to Disease
MH  - HLA-DP Antigens/*chemistry/*immunology
MH  - Haplotypes
MH  - Humans
MH  - Immunization
MH  - *Models, Molecular
MH  - Molecular Sequence Data
MH  - *Occupational Exposure
MH  - Risk Factors
MH  - Static Electricity
PMC - PMC1241746
EDAT- 2003/11/25 05:00
MHDA- 2004/03/10 05:00
PMCR- 2003/11/01
CRDT- 2003/11/25 05:00
PHST- 2003/11/25 05:00 [pubmed]
PHST- 2004/03/10 05:00 [medline]
PHST- 2003/11/25 05:00 [entrez]
PHST- 2003/11/01 00:00 [pmc-release]
AID - sc271_5_1835 [pii]
AID - 10.1289/ehp.6327 [doi]
PST - ppublish
SO  - Environ Health Perspect. 2003 Nov;111(15):1827-34. doi: 10.1289/ehp.6327.