DF/HCC Program Affiliation

Member, Cancer Immunology Program
Member, Invasion, Metastasis, and Angiogenesis Program

Research Abstract

This laboratory studies T lymphocyte biology with emphasis on antigen presentation, T cell receptor recognition, and lymphocyte homing and trafficking. We demonstrated that immune system T cells are capable of recognizing non-protein lipid and glycolipid antigens presented in the context of CD1 molecules. Thus, the paradigm that T cells recognize only peptide antigens in the context of MHC has been extended to reveal a further universe of foreign and self nonprotein antigens that are recognized in a CD1 restricted manner. Foreign microbial lipids and glycolipids are being studied in the context of vaccine development as their recognition plays an important role in eliciting a previously unappreciated component of T cell immunity in host defense. Studies on recognition of tumor glycolipids and the role of CD1 reactive NKT cells in tumor immunity are also being investigated. In addition, we are studying the role of cadherins in cell biology and cancer. Cadherins are cell adhesion and signaling molecules that are responsible for the morphogenesis of tissues during development and for their organization and integrity in adults. In addition, cadherins are critical molecules in cell transformation and cell behavior in cancer. We have found that a mesenchymal cadherin, cadherin-11, markedly enhances the migration and invasion of tumor cells. We are developing the reagents that block this molecule and reverse the increased invasiveness it mediates.

Publications

• Barral DC, Brenner MB. CD1 antigen presentation: how it works. Nat Rev Immunol 2007 Dec; 7(12):929-41
  PMID: 18037897
• Kiener HP, Stipp CS, Allen PG, Higgins JM, Brenner MB. The cadherin-11 cytoplasmic juxtamembrane domain promotes alpha-catenin turnover at adherens junctions and intercellular motility. Mol Biol Cell 2006 May; 17(5):2366-76
  PMID: 16525026
• van den Elzen P, Garg S, León L, Brigl M, Leadbetter EA, Gumperz JE, Dascher CC, Cheng TY, Sacks FM, Illarionov PA, Besra GS, Kent SC, Moody DB, Brenner MB. Apolipoprotein-mediated pathways of lipid antigen presentation. Nature 2005 Oct 6; 437(7060):906-10
  PMID: 16208376
• Moody DB, Young DC, Cheng TY, Rosat JP, Roura-Mir C, O'Connor PB, Zajonc DM, Walz A, Miller MJ, Levery SB, Wilson IA, Costello CE, Brenner MB. T cell activation by lipopeptide antigens. Science 2004 Jan 23; 303(5657):527-31
  PMID: 14739458
• Brigl M, Bry L, Kent SC, Gumperz JE, Brenner MB. Mechanism of CD1d-restricted natural killer T cell activation during microbial infection. Nat Immunol 2003 Dec; 4(12):1230-7
  PMID: 14578883