Binding domain regulation of MHC class II molecule assembly, trafficking, fate, and function.
Major histocompatibility complex class II molecules are heterodimeric type I integral membrane glycoproteins whose primary function is the capture of fragments of antigen in the endocytic pathway, and the presentation of these peptides to CD4+ alpha beta TCR-bearing T cells. The biochemical features of the class II peptide binding domain optimize it for this function by allowing interaction with denatured proteins prior to extensive degradation in endosomes and lysosomes. These same properties pose problems for alpha beta heterodimer assembly, avoidance of non-productive interactions with self-proteins, intracellular transport and dimer stability. This review discusses how coevolution of alpha and beta chain binding domain polymorphism and the extrinsic control of binding site function by invariant chain occupancy deal with these problems and permit the efficient functioning of the class II presentation system.
Germain
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Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-1892, USA.
D017951:Antigen Presentation; D000944:Antigens, Differentiation, B-Lymphocyte / Q000378:metabolism; D001665:Binding Sites; D001692:Biological Transport / Q000502:physiology; D004705:Endocytosis; D004721:Endoplasmic Reticulum / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis* / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D010455:Peptides / Q000502:physiology; D011485:Protein Binding / Q000276:immunology / Q000502:physiology; D011487:Protein Conformation
D000944:Antigens, Differentiation, B-Lymphocyte; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D010455:Peptides; C045084:invariant chain