MHC II molecules on antigen presenting cells present peptides to CD4 T cells delivering homeostatic signals (self-peptide) and initiating immune responses in case of infection (foreign peptides). In autoimmune conditions, immunological tolerance is broken and MHC II molecules loaded with self-peptides elicit the development of self-reactive T and B cells populations which lead to organ destruction. I am testing the hypothesis whether intrinsic structural factors of the MHC II molecule, such as protein stability, are the causal factor for the development of type 1 diabetes using heavy water labelling, a technology that we have developed in order to measure MHC protein turnover.
The MHC is the major genetic factor that determines susceptibility to autoimmunity, but in addition to genetic predisposition, environmental factors, such as intestinal microbiota, play a crucial role in the development of autoimmunity. My research interests are in understanding the cellular immunology mechanisms by which intestinal microbiota drive genetically susceptible organisms towards autoimmunity in particular in the context of type I diabetes.
cellular immunology ; T cell memory ; B cell receptor (BCR) ; B cells ; T cells ; MHC class II ; allotypes ; CD4+ ; microbiota ; antigen presentation ; HLA
Grimsholm O, Ren W, Bernardi AI, Chen H, Park G, Camponeschi A, Chen A, Bermann B, Hook N, Andersson S, Stromberg A, Gjertsson I, Cardell S, Yrlid U, De Riva A, Martensson IL .Absence of surrogate light chain results in spontaneous autoreactive germinal centres expanding VH81X-expressing B cells. Nat Commun. 2015 May 11;6:7077. doi: 10.1038/ncomms8077. Link Here
Alessandra De Riva, Mark C. Varley, Leslie J. Bluck, Anne Cooke, Michael J. Deery, and Robert Busch. Accelerated Turnover of MHC Class II Molecules in Nonobese Diabetic Mice Is Developmentally and Environmentally Regulated In Vivo and Dispensable for Autoimmunity J Immunol. 2013 Jun 15;190(12):5961-71.
Busch R, De Riva A, Hadjinicolaou AV, Jiang W, Hou T, Mellins ED. On the perils of poor editing: regulation of peptide loading by HLA-DQ and H2-A molecules associated with celiac disease and type 1 diabetes. Expert Rev Mol Med. 2012 Jul 6;14:e15.
De Riva A, Deery MJ, McDonald S, Lund T, Busch R. Measurement of protein synthesis using heavy water labeling and peptide mass spectrometry: Discrimination between major histocompatibility complex allotypes. Anal Biochem. 2010 Aug;403(1-2):1-12.
Keenan RA, De Riva A, Corleis B, Hepburn L, Licence S, Winkler TH, Mårtensson IL. Censoring of autoreactive B cell development by the pre-B cell receptor. Science. 2008 Aug 1;321(5889):696-9.
De Riva A, Bourgeois C, Kassiotis G, Stockinger B. Noncognate interaction with MHC class II molecules is essential for maintenance of T cell metabolism to establish optimal memory CD4 T cell function. J Immunol. 2007 May 1;178(9):5488-95.