[Frontiers in Bioscience S4, 1325-1332, June 1, 2012]

How HLA-DM molecules work: recognition of MHC II conformational heterogeneity

Scheherazade Sadegh-Nasseri1,2, Chih-Ling Chou2,3, Isamu Z. Hartman2,3, AeRyon Kim2, Kedar Narayan2,5

1Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205 USA, 2Graduate Program in Immunology, 3Department of Pharmacology and Toxicology, University of Arizona, Tucson AZ USA, 4Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX, USA, 5Biophysics Section, Laboratory of Cell Biology, National Cancer Institute, Bethesda, MD 20892

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. MHC class II synthesis and assembly with chaperones
4. Biochemical and structural characterization of DM
5. The molecular mechanism of DM function
5.1. Contribution of H-bonds to DM susceptibility of MHC class II-peptide complex
5.2. DM recognition of MHC class II conformation
6. A unifying model to explain mechanism of action of DM: a "hit-and-hug, then run" mechanism might explain how DM works!
7. A role for DM in epitope selection and immunodominance
8. Acknowledgements
9. References

1. ABSTRACT

Helper T cells respond to peptide antigens derived from exogenous sources presented by MHC II on antigen presenting cells. Antigens from pathogens are internalized by professional antigen presenting cells (APC) and processed for presentation. Certain epitopes are selected during processing as the final peptides for stimulation of T cells and are termed "immunodominant". Understanding how selection of immunodominant epitopes takes place has been a difficult task because of the complexity of the mechanisms governing both antigen processing and T cell recognition. In this review, we discuss our current understanding of HLA-DM function in peptide exchange and selection and its relevance to epitope immunodominance.