Immunologic Research

, Volume 47, Issue 1–3, pp 56–64 | Cite as

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

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


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.


MHC class II Kinetics Conformational heterogeneity Immunodominance H-bonds Peptide-receptive conformation 



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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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Scheherazade Sadegh-Nasseri
    • 1
  • Sateesh Natarajan
    • 2
    • 1
  • Chih-Ling Chou
    • 3
    • 1
  • Isamu Z. Hartman
    • 4
    • 1
  • Kedar Narayan
    • 5
    • 1
  • AeRyon Kim
    • 1
  1. 1.Department of PathologyJohns Hopkins University School of MedicineBaltimoreUSA
  2. 2.DendreonSeattleUSA
  3. 3.Program in NeuroscienceThe University of Arizona, College of PharmacyTucsonUSA
  4. 4.Department of Molecular GeneticsUniversity of Texas Southwestern Medical CenterDallasUSA
  5. 5.Laboratory of Cell BiologyNCI, NIHBethesdaUSA

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