The pathway for MHCII-mediated presentation of endogenous proteins involves peptide transport to the endo-lysosomal compartment. Export

@article{citeulike:1243592, abstract = {Antigen-presenting cells (APCs) are expected to present peptides from endocytosed proteins via major histocompatibility complex (MHC) class II (MHCII) molecules to T cells. However, a large proportion of peptides purified from MHCII molecules are derived from cytosolic self-proteins making the pathway of cytosolic peptide loading onto MHCII of critical relevance in the regulation of immune self-tolerance. We show that peptides derived from cytoplasmic proteins either introduced or expressed in the cytoplasm are first detectable as MHCII-peptide complexes in LAMP-1(+) lysosomes, prior to their delivery to the cell surface. These peptide-MHC complexes are formed in a variety of APCs, including peritoneal macrophages, dendritic cells, and B cells, and are able to activate T cells. This process requires invariant chain (Ii)-dependent sorting of MHCII to the lysosome and the activity of the molecular chaperone H-2M. This pathway is independent of the ER resident peptide transporter complex TAP and does not take place by cross-presentation from neighbouring cells. In conjunction with our earlier results showing that these peptides are derived by cytosolic processing via the proteasome, these observations provide evidence for a ubiquitous route for peptide transport into the lysosome for the efficient presentation of endogenous and cytoplasmic proteins to CD4 T cells.}, address = {National Centre for Biological Sciences, UAS-GKVK Campus, Bellary Road, Bangalore 560065, India.}, author = {Dani, A. and Chaudhry, A. and Mukherjee, P. and Rajagopal, D. and Bhatia, S. and George, A. and Bal, V. and Rath, S. and Mayor, S.}, citeulike-article-id = {1243592}, citeulike-linkout-0 = {http://dx.doi.org/10.1242/jcs.01288}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/15316082}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=15316082}, day = {15}, doi = {10.1242/jcs.01288}, issn = {0021-9533}, journal = {J Cell Sci}, keywords = {antigen-processing, mhc-class-ii}, month = {August}, number = {Pt 18}, pages = {4219--4230}, posted-at = {2007-04-22 14:33:08}, priority = {4}, title = {The pathway for MHCII-mediated presentation of endogenous proteins involves peptide transport to the endo-lysosomal compartment.}, url = {http://dx.doi.org/10.1242/jcs.01288}, volume = {117}, year = {2004} }

TY - JOUR ID - citeulike:1243592 L3 - citeulike-article-id:1243592 N2 - Antigen-presenting cells (APCs) are expected to present peptides from endocytosed proteins via major histocompatibility complex (MHC) class II (MHCII) molecules to T cells. However, a large proportion of peptides purified from MHCII molecules are derived from cytosolic self-proteins making the pathway of cytosolic peptide loading onto MHCII of critical relevance in the regulation of immune self-tolerance. We show that peptides derived from cytoplasmic proteins either introduced or expressed in the cytoplasm are first detectable as MHCII-peptide complexes in LAMP-1(+) lysosomes, prior to their delivery to the cell surface. These peptide-MHC complexes are formed in a variety of APCs, including peritoneal macrophages, dendritic cells, and B cells, and are able to activate T cells. This process requires invariant chain (Ii)-dependent sorting of MHCII to the lysosome and the activity of the molecular chaperone H-2M. This pathway is independent of the ER resident peptide transporter complex TAP and does not take place by cross-presentation from neighbouring cells. In conjunction with our earlier results showing that these peptides are derived by cytosolic processing via the proteasome, these observations provide evidence for a ubiquitous route for peptide transport into the lysosome for the efficient presentation of endogenous and cytoplasmic proteins to CD4 T cells. IS - Pt 18 JF - J Cell Sci SN - 0021-9533 AD - National Centre for Biological Sciences, UAS-GKVK Campus, Bellary Road, Bangalore 560065, India. EP - 4230 TI - The pathway for MHCII-mediated presentation of endogenous proteins involves peptide transport to the endo-lysosomal compartment. VL - 117 SP - 4219 KW - antigen-processing KW - mhc-class-ii AU - Dani, A AU - Chaudhry, A AU - Mukherjee, P AU - Rajagopal, D AU - Bhatia, S AU - George, A AU - Bal, V AU - Rath, S AU - Mayor, S PY - 2004/08/15/ UR - http://dx.doi.org/10.1242/jcs.01288 ER -