Variations in MHC Class II Antigen Processing and Presentation in Health and Disease

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  • Emil R. Unanue
    Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri 63110;
  • Vito Turk
    Department of Biochemistry and Molecular and Structural Biology, J. Stefan Institute, SI-1000 Ljubljana, Slovenia;
  • Jacques Neefjes
    Division of Cell Biology, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands;

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<jats:p>MHC class II (MHC-II) molecules are critical in the control of many immune responses. They are also involved in most autoimmune diseases and other pathologies. Here, we describe the biology of MHC-II and MHC-II variations that affect immune responses. We discuss the classic cell biology of MHC-II and various perturbations. Proteolysis is a major process in the biology of MHC-II, and we describe the various components forming and controlling this endosomal proteolytic machinery. This process ultimately determines the MHC-II–presented peptidome, including cryptic peptides, modified peptides, and other peptides that are relevant in autoimmune responses. MHC-II also variable in expression, glycosylation, and turnover. We illustrate that MHC-II is variable not only in amino acids (polymorphic) but also in its biology, with consequences for both health and disease.</jats:p>

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