FUCTIONAL SIGNIFICANCE OF THE DQA1*0501 ALLELE IN JDMS

  • Reed, Ann M (PI)

Project: Research project

Project Details

Description

Juvenile dermatomyositis (JDMS) is a systemic disorder characterized by
an inflammatory myopathy and vasculitis. The pathogenesis of JDMS is
hypothesized to be an autoimmune process which is induced by a viral
illness in a genetically susceptible individual. We have demonstrated
genetic susceptibility in JDMS by identifying an increased frequency of
the major histocompatibility complex (MHC) class II antigen HLA-
DQA1*0501. This information, my research interest and experience as well
as the ability to obtain subjects with this unusual and yet homogenous
autoimmune process allows the ideal environment to pursue the questions
below. The identification of the HLA-DQA1*0501 allele as a susceptibility gene,
allows us to determine the functional significance of this molecule with
respect to peptide binding and T- cell receptor (TCR) interactions.
Structural analysis has begun with nucleotide sequencing of the HLA-
DQA1*0501 gene. Functional analysis can be determined by creating a
panel of (APC) lines that display class II molecules with allelic
variations, evaluation of these APC lines' alloreactive T cells and in
the presentation of antigenic peptides. By having the ability to investigate a group of patients who have a
homogeneous autoimmune process with a recognized increase in a specific
HLA antigen, suggested to be the susceptibility allele, we have an ideal
study population from which we can effectively study a susceptibility
gene; in structure (by determining the HLA-DQA1*0501 sequence); and
function (by determining the restriction elements used by antigen
specific T cells in relationship to the HLA-DQA1*0501 allele and by
determining differences in the T cell response of JDMS and controls in
response to allelic variations). This investigation under the guidance
of Dr Frelinger, who not only has the facilities but also the expertise
in the area of HLA structure and function, gives the ideal environment
for which to successfully become an independent investigator while
addressing an important immunologic related autoimmune disease question.
StatusFinished
Effective start/end date9/30/938/31/99

Funding

  • National Institutes of Health: $85,993.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $87,303.00

ASJC

  • Medicine(all)

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