Hybrid membrane IgM with the transmembrane region of I-A alpha facilitates enhanced presentation of distinct epitopes to T cells.
The role of B cell Ag receptors (membrane Ig or mIg) in the efficient Ag presentation to T cells, including the requirement of mIgM-associated Ig alpha/Igbeta, remains unclear. We report here that mIgM, substituted with greater than two-thirds of the NH2-terminal A alpha transmembrane (TM) regions of the MHC class II molecule, are capable of mediating the efficient presentation of specific Ag to some (Group 1) but not all (Group 2) T cell hybridomas. In contrast, the generation of epitopes recognized by the Group 2 hybridomas can be mediated only by the wild-type mIgM. Tyrosine phosphorylation appears to be necessary for the enhanced Ag presentation to Group 2 hybridomas, while it does not for Group 1 hybridomas. In addition, differential sensitivity of Ag processing to leupeptin, different duration required for epitope generation/presentation, as well as the involvement of distinct epitopes for stimulation of these groups of T cell hybridomas were observed. These results suggest that transport of the mIgM/Ag complexes to an endocytic compartment(s) for generation of certain T cell epitopes may be mediated by the N-terminal TM sequence of mIgM, independent of Ig alpha/Igbeta association. This function can be replaced by two-thirds of the NH2-terminal TM region of A alpha chain of class II molecules.
Liu
K J
KJ
Department of Microbiology-Immunology, Northwestern University Medical School, Chicago, IL 60611, USA.
Schwen
M
M
Tucker
P W
PW
Kim
B S
BS
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects / Q000235:genetics; D016227:Benzoquinones; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000939:Epitopes / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D006825:Hybridomas; D007075:Immunoglobulin M / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D047029:Lactams, Macrocyclic; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D011809:Quinones / Q000494:pharmacology; D017828:Rifabutin / Q000031:analogs & derivatives; D013601:T-Lymphocytes / Q000276:immunology*
D016227:Benzoquinones; D004791:Enzyme Inhibitors; D000939:Epitopes; D000949:Histocompatibility Antigens Class II; D007075:Immunoglobulin M; D047029:Lactams, Macrocyclic; D011809:Quinones; D017828:Rifabutin; C020754:herbimycin