Albert Bendelac, MD, PhD

Professor
Chairman, Committee on Immunology
Investigator, Howard Hughes Medical Institute

Contact

Department of Pathology
The University of Chicago
929 East 57th Street
Gordon Center for Integrative Science Room W-506
Chicago, IL 60637

Tel: 773 834-8646
Fax: 773 834-1999
abendela@bsd.uchicago.edu


Research Interest

CD1-mediated Antigen Presentation.
In parallel with the MHC antigen presentation pathway, which presents protein antigens to T lymphocytes, the CD1 pathway evolved to present lipid antigens. Because, microbes can rapidly mutate their proteins but not their lipids to evade immune recognition, these complementary strategies respond to different evolutionary pressures. Our laboratory is exploring the biochemistry and cell biology of glycolipid antigen processing and presentation by CD1 molecules and the development, diversity and functions of glycolipid-specific T cells, We have mapped several steps of the intra-cellular pathway of CD1 trafficking and uncovered critical genes involved in antigen processing and presentation in the endosomal compartment. Most exciting is our recent discovery, in close interdisciplinary collaboration with colleagues at Scripps Research Institute and Brigham Young University, that saposins and other lipid transfer proteins play crucial functions in assisting lipid exchange between membrane compartments and CD1. 

We have also discovered that, in contrast with MHC-specific T cells, many T cells with CD1-specific T cell receptors follow a developmental pathway leading to a hybrid NK/T lineage. By developing fluorescent CD1 tetramers to label these cells, we were able to physically track their developmental pathway at the single cell level and explore the cellular interactions and signaling pathways involved. We are creating various transgenic models in vivo in mice and in vitro in organ culture systems, to further dissect the mechanisms underlying the development and the function of glycolipid-specific T cells. 

By enhancing our understanding of the mechanisms underlying glycolipid recognition by T cells, these studies might lead to various clinical applications. The conservation of CD1 genes across species and the limited ability of microbes to alter their lipids through gene mutation suggest that 'universal' glycolipid-based vaccines and adjuvants might be developed in the near future. In addition, CD1 regulates the immune rejection of cancer and appear to prevent type I diabetes, providing exciting avenues for basic as well as clinically applied research. 

Type I Diabetes
Type I diabetes is a disease of world-wide importance, affecting 1% of the American population during their lifetime, particularly in childhood. The disease is caused by T cells that are aberrantly directed against self-antigens expressed by insulin-producing cells in the pancreas, a breakdown of tolerance to self. We are studying the non-obese diabetic (NOD) mouse strain, which spontaneously expresses type I diabetes by 12-24 weeks of age. We found that disease could be transferred upon injection of T cells from diabetic mice into younger healthy recipients, and that full blown diabetes required both CD4 and CD8 T cells. We are focusing on two aspects of the disease process that might be amenable to immune intervention in order to prevent disease. Firstly, we are studying the diabetogenic CD8 T cells, the only cell-type that can directly interact with the insulin-producing cells, likely therefore to be the key downstream agent of this complex autoimmune process. Secondly, we are studying the role of CD1-restricted NKT cells, whose recruitment appears to protect against disease. These approaches might lead to novel strategies aiming at predicting and preventing disease in genetically predisposed individuals.