Antigen endocytosis and presentation mediated by human membrane IgG1 in the absence of the Ig(alpha)/Ig(beta) dimer.
Membrane immunoglobulin (mIg) M and D heavy chains possess minimal (KVK) cytoplasmic tails and associate with the Ig alpha/Ig beta (CD79) dimer to achieve surface expression and antigen presentation function. In contrast, the cytoplasmic tail of mIgG is extended by 25 residues (gamma ct). We have tested the possibility that mIgG can perform antigen capture and presentation functions independently of the Ig(alpha)/beta dimer. We show that CD4/(gamma)ct chimeras are efficiently endocytosed partially dependent on a tyrosine residue in (gamma)ct. In addition, human mIgG was expressed on the surface of Ig(alpha)/Ig(beta)-negative non-lymphoid cells and mediated antigen capture and endocytosis. Antigen-specific human mIgG targeted antigen to MIIC-type vesicles in the Ig(alpha)/beta negative melanoma Mel JuSo and augmented antigen presentation 1000-fold, identical to the augmentation seen in Ig(alpha)/beta-positive B-cells expressing the same transfected mIgG. Thus, unlike mIgM, mIgG has autonomous antigen capture and presentation capacity, which may have evolved to reduce or eliminate the BCR's dependence on additional accessory molecules.
Knight
A M
AM
Department of Biochemistry, Medical Sciences Institute, University of Dundee, UK.
Lucocq
J M
JM
Prescott
A R
AR
Ponnambalam
S
S
Watts
C
C
D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation; D015703:Antigens, CD / Q000276:immunology*; D015704:CD4 Antigens / Q000276:immunology; D051925:CD79 Antigens; D016466:CHO Cells; D002461:Cell Line, Transformed; D002462:Cell Membrane / Q000276:immunology; D006224:Cricetinae; D003593:Cytoplasm; D019281:Dimerization; D004705:Endocytosis; D006367:HeLa Cells; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D007143:Immunoglobulin Heavy Chains / Q000276:immunology; D007142:Immunoglobulin gamma-Chains / Q000276:immunology; D008969:Molecular Sequence Data; D011947:Receptors, Antigen, B-Cell / Q000276:immunology*; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D015704:CD4 Antigens; D051925:CD79 Antigens; C497881:CD79A protein, human; C497883:CD79B protein, human; D007074:Immunoglobulin G; D007143:Immunoglobulin Heavy Chains; D007142:Immunoglobulin gamma-Chains; D011947:Receptors, Antigen, B-Cell