With Regards To MHC lessons I antigen presentation, cTECs reveal a unique catalytic subunit of the proteasome described as I?5t
Proteasomes that incorporate I?5t include referred to as a€?thymoproteasomesa€™. They have a substrate desires that’s specific from proteasomes that contain the I?5 or I?5i subunits 4 (termed a€?housekeeping proteasomesa€™ and a€?immunoproteasomesa€™, respectively). Mice missing thymoproteasomes program an amazing defect in positive collection of CD8 + T cells 5 .
When it comes to MHC course II antigen speech, cTECs show the initial lysosomal proteases cathepsin L and thymus-specific serine protease (TSSP). Deficiency in these proteases results in impaired choice of CD4 + T cells. Cathepsin L-deficient rats reveal a highly diminished polyclonal CD4 + T mobile repertoire when you look at the thymus 6 , whereas TSSP deficient mice has typical polyclonal CD4 + T cell rates, yet showcase flawed positive variety of specific MHC course II-restricted transgenic TCRs as well as changed antigen-specific CD4 + T mobile feedback 7 . Furthermore, cTECs showcase an unusually high rate of constitutive macroautophagy, a mechanism that can offer the a€?unconventionala€™ running of peptides onto MHC lessons II molecules via an endogenous path 8 . Positive selection of several MHC course II-restricted transgenic TCRs was actually changed upon disturbance with macroautophagy in thymic epithelium, similar to the idea that autophagy types the MHC lessons II ligandome of cTECs 9 . (mais…)