In vivo and in vitro formation and dissociation of HLA-DR complexes with invariant chain-derived peptides.
HLA-DR molecules associated with class II-associated invariant chain peptides (CLIP) are generated in vivo as an intermediate in class II maturation. Such complexes can be produced in vitro by proteolytic digestion of DR alpha beta I complexes, suggesting that CLIP is a residual fragment that remains associated with class II molecules following I chain degradation. In vitro, CLIP dissociation from DR alpha beta dimers occurs at different rates depending on the allele, and is facilitated by low pH and by detergents containing 8-10 carbon unbranched hydrocarbons, or by primary aliphatic amines or carboxylic acids. The accumulation of DR alpha beta CLIP complexes in HLA-DM-negative antigen-processing mutant cells argues that a functionally similar mechanism, dependent on HLA-DM expression, catalyzes in vivo CLIP dissociation and generation of normal class II-peptide complexes.
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Section of Immunobiology, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut 06510.
Cresswell
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D000483:Alleles; D000595:Amino Acid Sequence; D000944:Antigens, Differentiation, B-Lymphocyte; D001665:Binding Sites; D002460:Cell Line; D018014:Gene Transfer Techniques; D006684:HLA-DR Antigens / Q000235:genetics / Q000378:metabolism*; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D008969:Molecular Sequence Data; D009154:Mutation; D011485:Protein Binding
D000944:Antigens, Differentiation, B-Lymphocyte; D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II; C045084:invariant chain