TY - JOUR
T1 - The alloreactive and self-restricted CD4+ T cell response directed against a single MHC class II/peptide combination
AU - Kovalik, Jean Paul
AU - Singh, Nagendra
AU - Mendiratta, Sanjeev K.
AU - Martin, W. David
AU - Ignatowicz, Leszek
AU - Van Kaer, Luc
PY - 2000/8/1
Y1 - 2000/8/1
N2 - The cellular basis for allograft rejection derives from the strong T cell response to cells bearing foreign MHC. While it was originally assumed that alloreactive T cells focus their recognition on the polymorphic residues that differ between syngeneic and allogeneic MHC molecules, studies with MHC class I-restricted CTL have shown that MHC-bound peptides play a critical role in allorecognition. It has been suggested that alloreactive T cells depend more strongly on interactions with the MHC molecule than with the associated peptide, but there is little evidence to support this idea. Here we have studied the alloreactive and self-restricted response directed against the class II H2-A(b) molecule bound with a single peptide, Ep, derived from the H2-Eα chain. This MHC class II-peptide combination was a poor target and stimulator of alloreactive CD4+ T cell responses, indicating that MHC-bound peptides are as important for alloreactive CD4+ T cells as they are for alloreactive CTL. We also generated alloreactive T cells with exquisite specificity for the A(b)/Ep complex, and compared their reactivity with self-restricted T cells specific for the same A(b)/Ep complex. Our results showed that peptide-specific alloreactive T cells, as compared with self-restricted T cells, were more sensitive to peptide stimulation, but equally sensitive to amino acid substitutions in the peptide. These findings indicate that alloreactive and self-restricted T cells interact similarly with their MHC/peptide ligand.
AB - The cellular basis for allograft rejection derives from the strong T cell response to cells bearing foreign MHC. While it was originally assumed that alloreactive T cells focus their recognition on the polymorphic residues that differ between syngeneic and allogeneic MHC molecules, studies with MHC class I-restricted CTL have shown that MHC-bound peptides play a critical role in allorecognition. It has been suggested that alloreactive T cells depend more strongly on interactions with the MHC molecule than with the associated peptide, but there is little evidence to support this idea. Here we have studied the alloreactive and self-restricted response directed against the class II H2-A(b) molecule bound with a single peptide, Ep, derived from the H2-Eα chain. This MHC class II-peptide combination was a poor target and stimulator of alloreactive CD4+ T cell responses, indicating that MHC-bound peptides are as important for alloreactive CD4+ T cells as they are for alloreactive CTL. We also generated alloreactive T cells with exquisite specificity for the A(b)/Ep complex, and compared their reactivity with self-restricted T cells specific for the same A(b)/Ep complex. Our results showed that peptide-specific alloreactive T cells, as compared with self-restricted T cells, were more sensitive to peptide stimulation, but equally sensitive to amino acid substitutions in the peptide. These findings indicate that alloreactive and self-restricted T cells interact similarly with their MHC/peptide ligand.
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U2 - 10.4049/jimmunol.165.3.1285
DO - 10.4049/jimmunol.165.3.1285
M3 - Article
C2 - 10903728
AN - SCOPUS:0034254298
SN - 0022-1767
VL - 165
SP - 1285
EP - 1293
JO - Journal of Immunology
JF - Journal of Immunology
IS - 3
ER -