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Conformational heterogeneity of MHC class II induced upon binding to different peptides is a key regulator in antigen presentation and epitope selection

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Abstract

T cells bearing αβ receptors recognize antigenic peptides bound to class I and class II glycoproteins encoded in the major histocompatibility complex (MHC). Cytotoxic and helper T cells respond respectively to peptide antigens derived from endogenous sources presented by MHC class I, and exogenous sources presented by MHC II, on antigen presenting cells. Differences in the MHC class I and class II structures and their maturation pathways have evolved to optimize antigen presentation to their respective T cells. A main focus of our laboratory is on efforts to understand molecular events in processing of antigen for presentation by MHC class II. The different stages of MHC class II—interactions with molecular chaperons involved in folding and traffic from the ER through the antigen-loading compartments, peptide exchange, and transport to the cell surface have been investigated. Through intense research on biophysical and biochemical properties of MHC class II molecules, we have learned that the conformational heterogeneity of MHC class II induced upon binding to different peptides is a key regulator in antigen presentation and epitope selection, and a determinant of the ability of MHC class II to participate in peptide association or dissociation and interaction with the peptide editor HLA-DM.

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Acknowledgments

SS-N wishes to specially thank Dr. Harden McConnell for his remarkable mentorship and for rightfully pointing out the importance of kinetic experiments. Funding for the research described here was from Cancer Research Institute, NIAID and NIGM. This work was supported by R01GM53549 and R01AI063764 grants to SS-N.

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Author notes

  1. Sateesh Natarajan

    Present address: Dendreon, Seattle, WA, USA

  2. Chih-Ling Chou

    Present address: Program in Neuroscience, The University of Arizona, College of Pharmacy, Tucson, AZ, 85721, USA

  3. Isamu Z. Hartman

    Present address: Department of Molecular Genetics, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX, 75390-9046, USA

  4. Kedar Narayan

    Present address: Laboratory of Cell Biology, NCI, NIH, Bethesda, MD, 20892-4256, USA

Authors and Affiliations

  1. Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA

    Scheherazade Sadegh-Nasseri, Sateesh Natarajan, Chih-Ling Chou, Isamu Z. Hartman, Kedar Narayan & AeRyon Kim

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  1. Scheherazade Sadegh-Nasseri
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Correspondence to Scheherazade Sadegh-Nasseri.

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Sadegh-Nasseri, S., Natarajan, S., Chou, CL. et al. Conformational heterogeneity of MHC class II induced upon binding to different peptides is a key regulator in antigen presentation and epitope selection. Immunol Res 47, 56–64 (2010). https://doi.org/10.1007/s12026-009-8138-1

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