The invariant chain is a phosphorylated subunit of class II molecules.
The phosphorylation of the MHC, class II-associated invariant chain (gamma) is demonstrated in human B-lymphoblastoid, melanoma, and histiocytic lymphoma cell lines. Two-dimensional nonequilibrium gel electrophoresis of invariant chain and class II Ag immunoprecipitates isolated from [32P]orthophosphate-labeled cells demonstrates labeling of both free and class II-associated gamma, gamma s, and p41 forms of the invariant chain. The gamma 2/gamma 3 form of the invariant chain is not phosphorylated. Phosphoamino amino acid analysis of isolated invariant chain shows phosphorylation of serine residues. The isolation of invariant chain from 32P-labeled microsome preparations digested with proteinase K demonstrates that the phosphorylation occurs in the cytoplasmic tail. Limited proteolysis of [32P]orthophosphate-, [35S]cysteine-, and [35S]methionine-labeled invariant chain also indicates that the 32P-label is incorporated into the cytoplasmic domain. These results pinpoint serine residues at positions 9, 26, and 29 in the N-terminal cytoplasmic tail as potential sites for the phosphorylation of the invariant chain. Phosphorylation may be another mechanism by which the functions of invariant chain in class II-dependent immune responses are regulated.
Spiro
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Department of Immunology, Research Institute of Scripps Clinic, La Jolla, CA 92037.
Quaranta
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D000595:Amino Acid Sequence; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002460:Cell Line; D003593:Cytoplasm / Q000378:metabolism; D006681:HLA-D Antigens / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008213:Lymphocyte Activation; D008264:Macrophages / Q000378:metabolism; D008545:Melanoma / Q000378:metabolism; D010766:Phosphorylation; D011110:Polymorphism, Genetic; D012323:RNA Processing, Post-Transcriptional; D012694:Serine / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000378:metabolism
D006681:HLA-D Antigens; D012694:Serine