Role of alpha3 domain of class I MHC molecules in the activation of high- and low-avidity CD8+ CTLs Export

@article{citeulike:2970662, abstract = {CD8 can serve as a co-receptor or accessory molecule on the surface of CTL. As a co-receptor, CD8 can bind to the {alpha}3 domain of the same MHC class I molecules as the TCR to facilitate TCR signaling. To evaluate the role of the MHC class I molecule {alpha}3 domain in the activation of CD8+ CTL, we have produced a soluble 227 mutant of H-2Dd, with a point mutation in the {alpha}3 domain (Glu227[-\>]Lys). 227 mutant class I-peptide complexes were not able to effectively activate H-2Dd-restricted CD8 T cells in vitro, as measured by IFN-{gamma} production by an epitope-specific CD8+ CTL line. However, the 227 mutant class I-peptide complexes in the presence of another MHC class I molecule (H-2Kb) (that cannot present the peptide) with a normal {alpha}3 domain can induce the activation of CD8+ CTL. Therefore, in order to activate CD8+ CTL, the {alpha}3 domain of MHC class I does not have to be located on the same molecule with the {alpha}1 and {alpha}2 domains of MHC class I. A low-avidity CD8+ CTL line was significantly less sensitive to stimulation by the 227 mutant class I-peptide complexes in the presence of the H-2Kb molecule. Thus, low-avidity CTL may not be able to take advantage of the interaction between CD8 and the {alpha}3 domain of non-presenting class I MHC molecules, perhaps because of a shorter dwell time for the TCR-MHC interaction. 10.1093/intimm/dxm111}, author = {Belyakov, Igor M. and Kozlowski, Steven and Mage, Michael and Ahlers, Jeffrey D. and Boyd, Lisa F. and Margulies, David H. and Berzofsky, Jay A.}, citeulike-article-id = {2970662}, citeulike-linkout-0 = {http://dx.doi.org/10.1093/intimm/dxm111}, citeulike-linkout-1 = {http://intimm.oxfordjournals.org/cgi/content/abstract/19/12/1413}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/17981793}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=17981793}, day = {1}, doi = {10.1093/intimm/dxm111}, journal = {Int. Immunol.}, keywords = {avidity}, month = {December}, number = {12}, pages = {1413--1420}, posted-at = {2008-07-07 18:44:03}, priority = {2}, title = {Role of {alpha}3 domain of class I MHC molecules in the activation of high- and low-avidity CD8+ CTLs}, url = {http://dx.doi.org/10.1093/intimm/dxm111}, volume = {19}, year = {2007} }

TY - JOUR ID - citeulike:2970662 L3 - citeulike-article-id:2970662 N2 - CD8 can serve as a co-receptor or accessory molecule on the surface of CTL. As a co-receptor, CD8 can bind to the {alpha}3 domain of the same MHC class I molecules as the TCR to facilitate TCR signaling. To evaluate the role of the MHC class I molecule {alpha}3 domain in the activation of CD8+ CTL, we have produced a soluble 227 mutant of H-2Dd, with a point mutation in the {alpha}3 domain (Glu227[->]Lys). 227 mutant class I-peptide complexes were not able to effectively activate H-2Dd-restricted CD8 T cells in vitro, as measured by IFN-{gamma} production by an epitope-specific CD8+ CTL line. However, the 227 mutant class I-peptide complexes in the presence of another MHC class I molecule (H-2Kb) (that cannot present the peptide) with a normal {alpha}3 domain can induce the activation of CD8+ CTL. Therefore, in order to activate CD8+ CTL, the {alpha}3 domain of MHC class I does not have to be located on the same molecule with the {alpha}1 and {alpha}2 domains of MHC class I. A low-avidity CD8+ CTL line was significantly less sensitive to stimulation by the 227 mutant class I-peptide complexes in the presence of the H-2Kb molecule. Thus, low-avidity CTL may not be able to take advantage of the interaction between CD8 and the {alpha}3 domain of non-presenting class I MHC molecules, perhaps because of a shorter dwell time for the TCR-MHC interaction. 10.1093/intimm/dxm111 IS - 12 JF - Int. Immunol. EP - 1420 TI - Role of {alpha}3 domain of class I MHC molecules in the activation of high- and low-avidity CD8+ CTLs VL - 19 SP - 1413 KW - avidity AU - Belyakov, Igor AU - Kozlowski, Steven AU - Mage, Michael AU - Ahlers, Jeffrey AU - Boyd, Lisa AU - Margulies, David AU - Berzofsky, Jay PY - 2007/12/01/ UR - http://dx.doi.org/10.1093/intimm/dxm111 ER -