T cell responses affected by aminopeptidase N (CD13)-mediated trimming of major histocompatibility complex class II-bound peptides.
Endocytosed protein antigens are believed to be fragmented in what appears to be a balance between proteolysis and MHC-mediated epitope protection, and the resulting peptide-MHC complexes are transported to the surface of the antigen-presenting cells (APC) and presented to T cells. The events that lead to antigenic peptide generation and the compartments where antigen processing takes place remains somewhat enigmatic. The importance of intracellular antigen processing has been well established; however, it is unclear whether additional processing occurs at the APC surface. To follow antigen processing, we have identified a pair of T cell hybridomas that recognize a long vs. a short version of the same epitope. We have used prefixed APC and various protease inhibitors to demonstrate that the APC surface has a considerable potential for antigen processing. Specific antibodies further identified the exopeptidase Aminopeptidase N (APN, CD13) as one of the enzymes involved in the observed cell-surface antigen processing. The NH2-terminal end of the longer peptide could, even while bound to major histocompatibility complex (MHC) class II molecules, be digested by APN with dramatic consequences for T cell antigen recognition. This could be demonstrated both in cell-free systems using purified reagents and in cellular systems. Thus, MHC class II and APN may act in concert to generate the final T cell epitopes.
Larsen
S L
SL
Department of Experimental Immunology, University of Copenhagen, Denmark.
Pedersen
L O
LO
Buus
S
S
Stryhn
A
A
D000595:Amino Acid Sequence; D000818:Animals; D000938:Antigen-Presenting Cells / Q000201:enzymology*; D018826:CD13 Antigens / Q000378:metabolism*; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D006825:Hybridomas; D008213:Lymphocyte Activation; D051379:Mice; D008969:Molecular Sequence Data; D009113:Muramidase / Q000737:chemistry / Q000276:immunology; D010455:Peptides / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*; D014407:Tumor Cells, Cultured
D000949:Histocompatibility Antigens Class II; D010455:Peptides; D009113:Muramidase; D018826:CD13 Antigens