In recent years several lines of research indicate the relevance of extracellular matrix remodeling in tissue homeostasis. Several enzymes, including matrix metalloproteinases (MMPs), have been described as modulators of tissue microenvironment through degradation of the extracellular matrix (in particular collagen metabolism), processing of cytokines and growth factors and processing of cellular surface receptors. The MMPs are the primary enzymes involved in collagenolysis. Peptide fragments generated by collagen processing could be presented to the immune system for generation of either tolerance or immunity.  In order to reveal new potential MHC class II restricted epitopes processed by MMPs that are distinct and additional to peptides processed by endosomal proteases, we developed peptidomics assays in which the antigen processing was coupled with nano-LC ESI MS/MS sequencing of the peptides epitopes.  New peptides derived from collagen-I and -II processing by the recombinant cathepsins S, B, D and L and by the late endosomal fraction isolated from dendritic cells (DCs) were sequenced and compared with the epitopes derived from the activity of pure recombinant MMPs (such as MMps 1-3 and 6-14)) and from the enzymatic activity of the plasma membrane fraction isolated from the human primary DCs, leading to the generation of new peptides epitopes (with molecular weights of 800-6,000 Da).  The new discovered epitopes suggest new mechanisms for the extracellular antigen processing distinct from those present in the late endosomal compartment.

Development of peptidomics assays to map the epitopes derived from collagen I and II processing by the late endosomes and by the plasma membrane of human primary dendritic cells

244th National Meeting (2012)

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