Search for NIOSH Publications: NIOSHTIC-2

NIOSHTIC-2 Search Results

Terms: 20023883

1 - 1 of 1 Bibliographic entries

All record(s) shown.

Save All   |   Save Page

View Saved    |    Download

 1

Electrostatic potential on human leukocyte antigen: implications for putative mechanism of chronic beryllium disease.

Authors

Snyder-JA; Weston-A; Tinkle-SS; Demchuk-E

Source

Environ Health Perspect 2003 Nov; 111(15):1827-1834

Link

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1241746/ 

NIOSHTIC No.

20023883 

Abstract

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.

Keywords

Leukocytes; Antigens; Beryllium-compounds; Beryllium-disease; Occupational-exposure; Epidemiology; Genes; Models; Genetic-factors; Heavy-metals

Contact

E. Demchuck, NIOSH, MS-3030, 1095 Willowdale Road, Morgantown, WV 26505, USA

CODEN

EVHPAZ

CAS No.

7440-41-7

Publication Date

20031101

Document Type

Journal Article

Email Address

edemchuck@cdc.gov

Fiscal Year

2004

NTIS Accession No.

NTIS Price

Issue of Publication

15

ISSN

0091-6765

NIOSH Division

HELD

Priority Area

Research Tools and Approaches: Risk Assessment Methods

Source Name

Environmental Health Perspectives

State

WV