Cristina Clement - An expanded self-antigen peptidome is carried by the human lymph as compared to the plasma.

Version 1

      Publication Details (including relevant citation   information):

      Clement CC, Cannizzo ES, Nastke MD, Sahu R,   Olszewski W, Miller NE, Stern LJ, Santambrogio L.

      PLoS One. 2010 Mar   26;5(3):e9863

      Abstract:

      BACKGROUND:

      The pre-nodal afferent lymph is the fluid which directly derives   from the extracellular milieu from every parenchymal organ and,   as it continues to circulate between the cells, it collects   products deriving from the organ metabolism/catabolism. A   comprehensive qualitative and quantitative investigation of the   self-antigenic repertoire transported by the human lymph is still   missing.

      METHODOLOGY/PRINCIPAL FINDINGS:

      A major difference between lymph and plasma could be visualized   by FPLC and 2D gel in the amount of low molecular weight products   corresponding to peptide fragments. Naturally processed peptides   in normal pre-nodal human lymph were then fractionated by HPLC   and characterized by multidimensional mass spectrometry. Analysis   of more then 300 sequences identified self-peptides derived from   both intracellular and extracellular proteins revealing the   variety of catabolic products transported by human lymph.   Quantitative analysis established that at least some of these   peptides are present in the circulating lymph in nanomolar   concentration.

      CONCLUSIONS/SIGNIFICANCE:

      The peptidome, generated by physiological tissue catabolism and   transported by the pre-nodal lymph, is in addition to the   self-peptidome generated in endosomal compartment. Unlike self   antigen processed by local or nodal APC, which mostly produce   epitopes constrained by the endosomal processing activity, self   antigens present in the lymph could derived from a wider variety   of processing pathways; including caspases, involved in cellular   apoptosis, and ADAM and other metalloproteinases involved in   surface receptor editing, cytokines processing and matrix   remodeling. Altogether, expanding the tissue-specific   self-repertoire available for the maintenance of immunological   tolerance.

      Address (URL): http://www.ncbi.nlm.nih.gov/pubmed/20360855