Antigen endocytosis and presentation mediated by human membrane IgG 1 in the absence of the

1984; Lanzavecchia, 1985). This is due to specific antigen Andrew M.Knight, John M.Lucocq1, binding, endocytosis and delivery for processing to the Alan R.Prescott, Sreenivasan Ponnambalam MHC class II-rich endosomal compartments (MIIC/CIIV) and Colin Watts found in these cells (Peters et al., 1991; Amigorena et al., Departments of Biochemistry and 1Anatomy and Physiology, Medical 1994; reviewed in Watts, 1997). The Igα/Igβ dimer has Sciences Institute, University of Dundee, Dundee, DD1 4HN, UK also been demonstrated to play an important role in BCR antigen presentation function. Since mIgM (μ) and mIgD Membrane immunoglobulin (mIg) M and D heavy (δ) have transmembrane heavy chains with only three chains possess minimal (KVK) cytoplasmic tails and putative cytoplasmic residues (–KVK), the Igα/Igβ dimer associate with the Igα/Igβ (CD79) dimer to achieve is thought to act as an adaptor permitting the external surface expression and antigen presentation function. antigen binding site to be internalized and access the In contrast, the cytoplasmic tail of mIgG is extended endocytic pathway. Indeed, the cytoplasmic domain of by 25 residues (γct). We have tested the possibility that Igβ was able to confer endocytosis and antigen presentation mIgG can perform antigen capture and presentation capacity when directly fused to mIg or Fc receptors (Patel functions independently of the Igα/β dimer. We show and Neuberger, 1993; Bonnerot et al., 1995), although in that CD4/γct chimeras are efficiently endocytosed parone study only the tail of Igα appeared able to target tially dependent on a tyrosine residue in γct. In addition, FcR-bound antigen to newly synthesized class II MHC human mIgG was expressed on the surface of Igα/Igβmolecules (Bonnerot et al., 1995). negative non-lymphoid cells and mediated antigen Following antigen stimulation and isotype switching, capture and endocytosis. Antigen-specific human mIgG B-cells continue to express membrane-anchored immunotargeted antigen to MIIC-type vesicles in the Igα/β globulins. However, the isotype-switched immunoglobulin negative melanoma Mel JuSo and augmented antigen classes IgG (γ), IgA (α) and IgE (ε) possess extended presentation 1000-fold, identical to the augmentation cytoplasmic tails encoded by the M2 exon (Bensmana and seen in Igα/β-positive B-cells expressing the same Lefranc, 1990; Kinoshita et al., 1991; Sun et al., 1991, transfected mIgG. Thus, unlike mIgM, mIgG has respectively). In the case of mIgG, the KVK sequence is autonomous antigen capture and presentation capacity, extended by 25 residues to form a cytoplasmic tail (γct) which may have evolved to reduce or eliminate the which is highly conserved among γ sub-types and between BCR’s dependence on additional accessory molecules. species (Bensmana and Lefranc, 1990; Kinoshita et al.,