TY - JOUR
T1 - Quantitative analysis of the contribution of TCR/pepMHC affinity and CD8 to T cell activation
AU - Holler, Phillip D.
AU - Kranz, David M.
N1 - Funding Information:
We thank S. Jameson and M. Daniels for the K b plasmid and advice on tetramer preparation, S. O'Herrin for the J558L hybridoma that expresses the L d -IgG1 fusion, the NIH Tetramer facility for several of the initial preparations of pepMHC tetramers, L. Teyton for insect cells and expression vector, J. Parnes for CD8α and β cDNA clones, L. Chlewicki for help in isolation of several of the mutant TCRs, B. Cho for assistance with initial transfections, A. Lim and L. Carr for assistance with IL-2 assays, and the staff of the UI Flow Facility for technical advice. Supported by NIH Grant RO1 GM55767.
PY - 2003/2/1
Y1 - 2003/2/1
N2 - The relative roles of CD8, TCR:pepMHC affinity, and TCR:pepMHC dissociation rate in T cell activation have remained controversial. To determine the relationships among these factors, we used T cells transfected with normal and in vitro engineered αβ TCRs, in the presence or absence of CD8. The TCRs exhibited a wide range of affinities (KD values of 80 μM to 5 nM). T cells with the highest affinity TCRs were efficiently stimulated by peptide, with or without CD8. In contrast, CD8 was required for T cells that expressed TCRs with affinities typical of syngeneic reactions (KD values above ∼3 μM). The results suggest that virtually all normal syngeneic interactions require CD8, which enhances peptide sensitivity by one million-fold or more.
AB - The relative roles of CD8, TCR:pepMHC affinity, and TCR:pepMHC dissociation rate in T cell activation have remained controversial. To determine the relationships among these factors, we used T cells transfected with normal and in vitro engineered αβ TCRs, in the presence or absence of CD8. The TCRs exhibited a wide range of affinities (KD values of 80 μM to 5 nM). T cells with the highest affinity TCRs were efficiently stimulated by peptide, with or without CD8. In contrast, CD8 was required for T cells that expressed TCRs with affinities typical of syngeneic reactions (KD values above ∼3 μM). The results suggest that virtually all normal syngeneic interactions require CD8, which enhances peptide sensitivity by one million-fold or more.
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U2 - 10.1016/S1074-7613(03)00019-0
DO - 10.1016/S1074-7613(03)00019-0
M3 - Article
C2 - 12594952
AN - SCOPUS:0037331525
SN - 1074-7613
VL - 18
SP - 255
EP - 264
JO - Immunity
JF - Immunity
IS - 2
ER -