Altered recognition of antigen is a mechanism of CD8+ T cell tolerance in cancer Export

@article{citeulike:1440308, abstract = {Antigen-specific CD8+ T-cell tolerance, induced by myeloid-derived suppressor cells (MDSCs), is one of the main mechanisms of tumor escape. Using in vivo models, we show here that MDSCs directly disrupt the binding of specific peptide-major histocompatibility complex (pMHC) dimers to CD8-expressing T cells through nitration of tyrosines in a T-cell receptor (TCR)-CD8 complex. This process makes CD8-expressing T cells unable to bind pMHC and to respond to the specific peptide, although they retain their ability to respond to nonspecific stimulation. Nitration of TCR-CD8 is induced by MDSCs through hyperproduction of reactive oxygen species and peroxynitrite during direct cell-cell contact. Molecular modeling suggests specific sites of nitration that might affect the conformational flexibility of TCR-CD8 and its interaction with pMHC. These data identify a previously unknown mechanism of T-cell tolerance in cancer that is also pertinent to many pathological conditions associated with accumulation of MDSCs.}, author = {Nagaraj, Srinivas and Gupta, Kapil and Pisarev, Vladimir and Kinarsky, Leo and Sherman, Simon and Kang, Loveleen and Herber, Donna L. and Schneck, Jonathan and Gabrilovich, Dmitry I.}, citeulike-article-id = {1440308}, citeulike-linkout-0 = {http://dx.doi.org/10.1038/nm1609}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/17603493}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=17603493}, day = {01}, doi = {10.1038/nm1609}, issn = {1078-8956}, journal = {Nature Medicine}, keywords = {cancer, cd8\_t\_cell, tania\_tb\_paper, tolerance}, month = {July}, number = {7}, pages = {828--835}, posted-at = {2008-07-26 04:26:20}, priority = {2}, publisher = {Nature Publishing Group}, title = {Altered recognition of antigen is a mechanism of CD8+ T cell tolerance in cancer}, url = {http://dx.doi.org/10.1038/nm1609}, volume = {13}, year = {2007} }

TY - JOUR ID - citeulike:1440308 L3 - citeulike-article-id:1440308 N2 - Antigen-specific CD8+ T-cell tolerance, induced by myeloid-derived suppressor cells (MDSCs), is one of the main mechanisms of tumor escape. Using in vivo models, we show here that MDSCs directly disrupt the binding of specific peptide-major histocompatibility complex (pMHC) dimers to CD8-expressing T cells through nitration of tyrosines in a T-cell receptor (TCR)-CD8 complex. This process makes CD8-expressing T cells unable to bind pMHC and to respond to the specific peptide, although they retain their ability to respond to nonspecific stimulation. Nitration of TCR-CD8 is induced by MDSCs through hyperproduction of reactive oxygen species and peroxynitrite during direct cell-cell contact. Molecular modeling suggests specific sites of nitration that might affect the conformational flexibility of TCR-CD8 and its interaction with pMHC. These data identify a previously unknown mechanism of T-cell tolerance in cancer that is also pertinent to many pathological conditions associated with accumulation of MDSCs. IS - 7 JF - Nature Medicine SN - 1078-8956 EP - 835 TI - Altered recognition of antigen is a mechanism of CD8+ T cell tolerance in cancer PB - Nature Publishing Group VL - 13 SP - 828 KW - cancer KW - cd8_t_cell KW - tania_tb_paper KW - tolerance AU - Nagaraj, Srinivas AU - Gupta, Kapil AU - Pisarev, Vladimir AU - Kinarsky, Leo AU - Sherman, Simon AU - Kang, Loveleen AU - Herber, Donna AU - Schneck, Jonathan AU - Gabrilovich, Dmitry PY - 2007/07/01/ UR - http://dx.doi.org/10.1038/nm1609 ER -