Richard G. Cook, Ph.D. - Faculty
Professor, Department of Pathology & Immunology
Ph.D., Case Western Reserve University
Postdoctoral, The University of Texas Southwestern Medical School
Structure and Function of Class I MHC Molecules
A major histocompatibility complex (MHC) is found in all vertebrate species and represents a cluster of tightly-linked genes that encode proteins involved in regulation of immune responses. There are two subsets of MHC-encoded class I proteins - I-a and I-b. The former are very polymorphic, expressed on all cells, and serve as “markers” of self and non-self. Each class I-a molecule binds a limited set of peptides based on the sequence of the peptide, and peptides derived from both self and foreign (viral, bacterial, etc.) proteins can bind. These complexes of class I molecules and peptide serve as ligands for the antigen-specific T cell receptor on T lymphocytes during developmental (self peptides) and effector (foreign peptides) phases of immune responses and can also be recognized by receptors on NK cells. Less is known regarding the function of the class I-b proteins, but evidence indicates they function similarly except with possibly more specialized and restricted functions (binding of N-formylated peptides, expression in the absence of bound peptide, activation of CD8 regulatory cells, recognition by NK cells, placental expression). Of the approximately 35 class I-b genes defined in the Q/T/M regions of the mouse MHC, only 8-10 have been found to encode functional proteins. They display much less polymorphism than class I-a proteins and several have a more restricted tissue distribution. The general focus of studies in this laboratory is on the evolution, structure/function relationships and mechanisms that regulate expression of MHC encoded class I-b molecules (TL, Qa-1 and HLA-E).
Dr. Cook is also Director of the BCM Advanced Technology Laboratories and Director of the Protein Chemistry/Proteomics Core Laboratory and Co-director of the Duncan Cancer Center Protein Expression and Proteomics Shared Resource. His research interests here are in providing scientific advice and technical assistance to and collaborating with numerous investigators in the general area of proteomics.
Davis, BK, RG Cook, RR Rich, JR Rodgers. Hyperconservation of the putative antigen recognition site of the MHC class I-b Molecule TL in the subfamily murinae: Evidence that thymus Leukemia antigen is an ancient mammalian gene. J. Immunol. 169:6890-6889, 2002.
Stahl, BD, PA Grant, SD Briggs, ZW Sun, ZW Sun, JR Bone, JA Caldwell, S Mollah, RG Cook, J Shabanowitz, DF Hunt, CD Allis. Set2 is a nucleosomal histone H3-selective methyltransferase that mediates transcriptional repression. Mol. Cell. Biol. 22(5):1298-1306, 2002.
Doyle, CK, BK Davis, RG Cook, RR Rich, JR Rodgers. Hyperconservation of the N-formyl peptide binding site of M3: Evidence that M3 is an old eutherian molecule with conserved recognition of a pathogen-associated molecular pattern. J. Immunol. 171(2):836-44, 2003.
Doyle, CK, RG Cook, RR Rich, JR Rodgers. Cotton rat Sihi-M3 is a minimally oligomorphic Mhc I-b molecule that binds the chemotactic peptide fMLF under stringent conditions: Evidence that positive selection drives inter-species diversity of residues interacting with termini of short peptides. Immunogenetics 55:389-394, 2003.
Wang, Y, J Wysocka, J Sayegh, Y-H Lee, JR Perlin, L Leonelli, LS Sonbuchner, CH McDonald, RG Cook, Y Dou, RG Roeder, S Clarke, MR Stallcup, CD Allis and SA Coonrod. Human PAD4 regulates histone arginine methylation levels via demethylimination. Science 306:279-283, 2004.
- Rodgers, JR and RG Cook. MHC class I-b molecules bridge innate and acquired immunity. Nature Reviews in Immunology 5:459-471, 2005.
- Benson, LJ, Y Gu, T Yakovleva, K Tong, C Barrows, CL Strack, RG Cook, CA Mizzen, and A T Annunziato. Modifications of H3 and H4 during chromatin replication, nucleosome assembly, and histone exchange. J. Biol. Chem., 281(14):9287-9296, 2006.
- Greenlee KJ, DB Corry, DA Engler, RK Matsunami, P Tessier, RG Cook, Z Werb, and F Kheradmand. Proteomic identification of in vivo substrates for matrix metalloproteinases 2 and 9 reveals a mechanism for resolution of inflammation. J Immunol. 177(10):7312-7321, 2006
- Choi, H, K. Aboulfatova, HJ Pownall, R Cook, and J-F Dong. Shear-induced disulfide bond formation regulates adhesion activity of von Willebrand Factor. J Biol Chem. 282:35604-35611, 2007.
To see a complete list of Dr. Cook's publications, visit PubMed.
Baylor College of Medicine
Department of Pathology & Immunology
One Baylor Plaza, BCM245
Houston, Texas 77030, U.S.A.