This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. MHC (major histocompatibility complex) molecules are highly polymorphic molecules which are critical in the self versus non-self discrimination of Immune system. The MHC molecules are comprised of two classes, namely MHC type I (comprised of HLA-A (Human leukocyte antigen), HLA-B and HLA-C molecules) and MHC type II molecules (HLA-DQ, HLA-DR and HLA-DP molecules) which have differing immune system functions. MHC molecules belonging to different families may vary from each other from as few as a couple of amino acids to greater than 30 amino acids. However, the HLA molecules in combination with the peptide presented is highly specific in the recognition of self versus non-self. The structural basis of the same is not well understood and remains a subject of much research. In addition the allelic distribution of these genes underscores the critical role played by the system in protection against microbial invaders of the body. The MHC system also forms the basis for autoimmune diseases whose mechanisms are not well understood. In this study we aim to understand the molecular mechanisms by which HLA micropolymorphisms influence the binding of a viral epitope to the MHC class I (HLA-B*44xx molecules). In addition, configurational information regarding the dynamic structure of the HLA-epitope complex will be analyzed to understand the basis of recognition by the TCR (T-cell receptor) which represents the second half of the antigen-antibody recognition puzzle. The study will use the technique of computational molecular dynamics to understand the role of critical amino acid binding residues in the cleft of HLA-B*44xx molecules. The dynamics of peptide flexibility and plasticity are hypothesized to play a critical role in the immune recognition which is a major focus of this study. We expect the study to provide a major understanding regarding the role of HLA-micropolymorphisms in the recognition and signalling of human immune molecules

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
3P41RR006009-20S1
Application #
8364304
Study Section
Special Emphasis Panel (ZRG1-BCMB-Q (40))
Project Start
2011-09-15
Project End
2013-07-31
Budget Start
2011-09-15
Budget End
2013-07-31
Support Year
20
Fiscal Year
2011
Total Cost
$1,094
Indirect Cost
Name
Carnegie-Mellon University
Department
Biostatistics & Other Math Sci
Type
Schools of Arts and Sciences
DUNS #
052184116
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
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