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Medicine; Dept. of Medicine - Rheumatology
Molecular Biology and Genetics
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1068 Ross Building
Baltimore MD 21205
Structure and function of the genes and gene products of the mammalian major histocompatibility complex
The binding and presentation of peptide fragments to T lymphocytes by histocompatibility molecules is a central event in regulating the immune response to self and non-self antigens. My group has focused on the study of a novel family of conserved class I histocompatibility proteins termed class Ib molecules. We have found that one member of this family, the Qa-1 molecule encoded by the class Ib gene T23, binds peptides derived from bacterial and mammalian stress (heat-shock) proteins. We have also determined that Qa-1 and plays an important role in the presentation of bacterial peptide epitopes to anti-bacterial CD8+ cytotoxic T lymphocytes in the immune response to gram negative pathogens. These observations suggest that this molecule serves a novel function relevant to the clearance of bacterial infections as well as the development of self-reactive T cells. Such molecules may be useful targets in the design of vaccines that evoke protective anti-bacterial immunity. We are currently using approaches which blend protein/peptide biochemistry, protein engineering, generation of novel transgenic animals and targeted mutagenesis to isolate and chemically characterize peptide epitopes bound to and presented by T23 and in identifying and functionally characterizing T cells which recognize antigens presented by these and related molecules. Also, we are devising strategies for the identification and characterization of their human counterparts. The goal is to understand under what physiological settings the immune system utilizes these conserved class Ib molecules in regulating responses and to determine if this information can lead to novel strategies for immune intervention.
Jiang H, Wu Y, Liang B, Zheng Z, Tang G, Kanellopoulos J, Soloski MJ, Winchester R, Goldstein I, Chess L. (2005) An affinity/avidity model of peripheral T cell regulation. J. Clin. Invest. 90:51-81.
Wooden SL, Kalb SR, Cotter RJ, Soloski MJ. (2005) Cutting Edge: HLA-E Binds a Peptide Derived from the ATP-Binding Cassette Transporter Multidrug Resistance-Associated Protein 7 and Inhibits NK Cell-Mediated Lysis. J. Immunol. 107(2):628-36.
Lo W-F, Dunn C.C, Ong H, Metcalf ES, and Soloski MJ. (2004) Bacterial and Host Factors Involved in the MHC class Ib-Restricted-Restricted Presentation of Salmonella Hsp 60: A Novel Pathway. Infection and Immunity 74(4):2495-7.
Davies A, Lopez-Briones S, Ong H, O’Neil-Marshall C, Lemonnier FA, Nagaraju K, Metcalf ES, and Soloski MJ. (2004) Infection Induced Expansion of A MHC Class Ib Dependent Intestinal Intraepithelial gd T Cell Subset. J. Immunol. 203(3):599-606.
Davies, A, Ramirez S, Liang B, Aldrich C, Lemonnier FA, Jiang,H. Cotter,R. and Soloski MJ. (2003) A Peptide from Heat Shock Protein 60 is the Dominant Peptide bound to Qa-1 in the absence of the MHC Class Ia Leader Sequence Peptide Qdm. J. Immunol. 36(5):1179-86.
Soloski MJ., and Metcalf EM. (2001) The Involvement of Class I Molecules in the Host Response to Infection with Salmonella and its Relevance to Autoimmuity. Microbes and Infection 28(1-2):15-24.
Lo W-F, Woods AS, DeCloux A, Cotter RJ, Metcalf ES and Soloski MJ. (2000) Molecular Mimicry Mediated by MHC Class Ib Molecules Following Infection with Gram-Negative Pathogens. Nature Medicine 116(1):163-73.