TY - JOUR
T1 - TCR specificity dictates CD94/NKG2A expression by human CTL
AU - Jabri, Bana
AU - Selby, Jeanette M.
AU - Negulescu, Horia
AU - Lee, Leanne
AU - Roberts, Arthur I.
AU - Beavis, Andrew
AU - Lopez-Botet, Miguel
AU - Ebert, Ellen C.
AU - Winchester, Robert J.
N1 - Funding Information:
The authors thank H. Vie for his advice in deriving human CTL clones, M. Bonneville for discussions, and A. Bendelac and L. Ferradini for discussions and critical reading of the manuscript. This work is supported by National Institutes of Health grants RO1 DK 58727-01A1 and DK 42166-11, ACE U19 AI46132, and grants FIS 00/0181 and SAF2001/0696.
PY - 2002/10/1
Y1 - 2002/10/1
N2 - Activating and inhibitory CD94/NKG2 receptors regulate CTL responses by altering TCR signaling, thus modifying antigen activation thresholds set during thymic selection. To determine whether their expression was linked to TCR specificity, we examined the TCR repertoire of oligoclonal CTL expansions found in human blood and tissues. High-resolution TCR repertoire analysis revealed that commitment to inhibitory NKG2A expression was a clonal attribute developmentally acquired after TCR expression and during antigen encounter, whereas actual surface expression depended on recent TCR engagement. Further, CTL clones expressing sequence-related TCR, and therefore sharing the same antigen specificity, invariably shared the same NKG2A commitment. These findings suggest that TCR antigenic specificity dictates NKG2A commitment, which critically regulates subsequent activation of CTL.
AB - Activating and inhibitory CD94/NKG2 receptors regulate CTL responses by altering TCR signaling, thus modifying antigen activation thresholds set during thymic selection. To determine whether their expression was linked to TCR specificity, we examined the TCR repertoire of oligoclonal CTL expansions found in human blood and tissues. High-resolution TCR repertoire analysis revealed that commitment to inhibitory NKG2A expression was a clonal attribute developmentally acquired after TCR expression and during antigen encounter, whereas actual surface expression depended on recent TCR engagement. Further, CTL clones expressing sequence-related TCR, and therefore sharing the same antigen specificity, invariably shared the same NKG2A commitment. These findings suggest that TCR antigenic specificity dictates NKG2A commitment, which critically regulates subsequent activation of CTL.
UR - http://www.scopus.com/inward/record.url?scp=0036799629&partnerID=8YFLogxK
U2 - 10.1016/S1074-7613(02)00427-2
DO - 10.1016/S1074-7613(02)00427-2
M3 - Article
C2 - 12387742
AN - SCOPUS:0036799629
SN - 1074-7613
VL - 17
SP - 487
EP - 499
JO - Immunity
JF - Immunity
IS - 4
ER -