John R. Rodgers, Ph.D. - Faculty
Associate Professor, Department of Pathology & Immunology
B.A., Swarthmore College, 1977
Ph.D., Baylor College of Medicine
Research Interests: Evolution and function of class I MHC genes
Current research focuses on the molecular and selective mechanisms of class I MHC evolution. Murid rodents carry a large number of class I-b genes that represent a natural laboratory for experimenting with class I structure and function; many of these never evolved in or were deleted from human ancestors. M3 encodes a molecule that binds N-formyl peptides- derived from mitochondria and from intracellular bacterial pathogens- and presents them to T cells. M3 appears to be an ancient molecule, possibly evolving before the mammalian radiation, and may represent a bridge between innate and acquired antigen recognition mechanisms. Exit of M3 from the endoplasmic reticulum is exceptionally dependent on ligand binding, so that increase of M3 at the cell surface may indicate bacterial infection. is another probably ancient molecule that appears to bind no peptide whatsoever, yet is recognized by T cells. Its function is a mystery, yet its ability to traffic to the cell surface in the absence of ligand binding provides a striking counter to the peptide-dependency of M3. We are interested in molecular mechanisms controlling MHC egress from the ER - a process critical to the function of all class I molecules.
The evolution of placental mammals required solving several gnarly immunological problems - "Medawar's paradox" - to avoid maternal immune rejection of the fetus. One of these was, apparently, to down-regulate the expression of polymorphic class I-a molecules in the placenta and extraembryonic tissues. Most cells that down-regulate class I are vulnerable to killing by natural killer cells - probably to prevent this mammals have evolved monomorphic class I genes expressed in the placenta Curiously, different lineages of mammals express very different placental class I molecules. We are studying one of these- H2-B1- a mouse MHC molecule expressed in the placenta, brain and small intestine.
Vyas, J. M., Rich, R. R., Howell, D. D., Shawar, S. M., and Rodgers, J. R. (1994). Availability of endogenous peptides limits expression of an M3a-Ld MHC class I chimera. J. Exp. Med. 179, 155-165.
Rodgers, J. R., Mehta, V., and Cook, R. G. (1995). Surface expression of ß2-microglobulin-associated thymus-leukemia antigen is independent of TAP2. Eur. J. Immunol. 25, 1001-1007.
Vyas, J. M., Rodgers, J. R., and Rich, R. R. (1995). H-2M3a violates the paradigm for MHC class I peptide binding. J. Exp. Med. 181, 1817-1825.
Howell, D, Levitt, JM, Foster, PA, Guenther, MM, Shawar, SMS, Rich, RR and Rodgers, JR (2000) Heterogeneity of RMA-S cell line: derivatives of RMA-S cells lacking H2-Kb and H2-Db expression. Immunogenetics 52:150-154.
Singh, RAK, Rodgers, JR and Barry, MA (2002) The role of T cell antagonism and original antigen sin in genetic immunization. J Immunol 1696779-6786.
Doyle, CK, Davis, BK, Cook, RG, Rich, RR and Rodgers, JR (2003) 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 171:836-844.
Davis, BK, Cook, RG, Rich, RR and Rodgers, JR (2002) 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 169:6890-6899.
Doyle, CK, Cook, RG, Rich, RR and Rodgers, JR (2003) 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 the termini of short peptides. Immunogenetics 55:389-394.
For a complete list of Dr. Rodgers' publications, visit PubMed.
John R. Rodgers, Ph.D.
Department of Pathology & Immunology
Baylor College of Medicine
One Baylor Plaza, BCM245
Houston, TX 77030