Modulation of antigen presentation and class II expression by a class II-associated invariant chain peptide.
During the process of MHC class II assembly, the class II-associated invariant chain peptide (CLIP) remains bound within the peptide binding groove until its subsequent removal, which is mediated by H-2 M. We have defined the functional role of CLIP, through saturation of the endosomal compartment with exogenous CLIP-(85-101), resulting in reduced class II MHC on the surface of APCs and an impeded T cell response. Conversely, incubation of the same cells with immunogenic peptides or proteins resulted in an up-regulation of surface class II MHC. T cells from CLIP- plus Ag-immunized mice showed a marked decrease in Ag-specific response over that in mice primed with Ag alone. A B cell hybridoma, TA3 (H-2d,k) incubated with CLIP in vitro showed dramatically reduced MHC class II I-A surface expression. APCs derived from CLIP-immunized mice exhibited down-regulation of surface class II MHC, but not of CD45 (B220). Electrophoretic studies showed that the addition of exogenous CLIP resulted in a relative decrease in SDS-stable MHC class II heterodimers in TA3 cells. Studies with FITC-CLIP and FITC-OVA-(323-339) peptides demonstrated that exogenously added CLIP peptide does not bind to surface class II molecules via the endogenous route, whereas OVA peptide does. This suggests that exogenously added CLIP acts intracellularly, perhaps in the compartment where H-2 M intersects with class II molecules. These findings demonstrate the functional role of CLIP to regulate MHC class II-mediated Ag presentation in CD4+ T cell responses.
Zechel
M A
MA
Department of Microbiology and Immunology, University of Western Ontario, London, Canada.
Chaturvedi
P
P
Lee-Chan
E C
EC
Rider
B J
BJ
Singh
B
B
D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation; D000944:Antigens, Differentiation, B-Lymphocyte / Q000235:genetics / Q000378:metabolism*; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002460:Cell Line; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000378:metabolism*; D006825:Hybridomas; D007114:Immunization; D066298:In Vitro Techniques; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008969:Molecular Sequence Data; D011485:Protein Binding; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
D000944:Antigens, Differentiation, B-Lymphocyte; D000949:Histocompatibility Antigens Class II; C045084:invariant chain