The Alloreactive and Self-Restricted CD4+ T Cell Response Directed Against a Single MHC Class II/Peptide Combination

Abstract

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-Ab 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 Ab/Ep complex, and compared their reactivity with self-restricted T cells specific for the same Ab/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.

A New T-Cell Receptor Transgenic Model of the CD4+ Direct Pathway: Level of Priming Determines Acute Versus Chronic Rejection

“…The 4C T cell has direct allospecificity against I-A d and appears to require an as yet undetermined peptide or peptides, consistent with previous reports showing that the vast majority of direct CD4 ϩ alloreactive responses are peptide dependent (17,18). The 4C T cells respond to an I-A d restricted motif present in skin, heart, and islet allografts (unpublished data).…”

Statins as a newly recognized type of immunomodulator

“…MLRs were performed as described 17 . Briefly, human ECs and Mφ were cultured on 96-well plates pretreated with the respective stimuli and irradiated.…”

Vaccination with Allogeneic Dendritic Cells Fused to Carcinoma Cells Induces Antitumor Immunity in MUC1 Transgenic Mice

“…Such interactions are probably due to the inherent affinity of TCRs for MHC molecules (28,29). Other studies have demonstrated that peptide-specific alloreactive T cells, compared with self-restricted T cells, are more sensitive to peptide stimulation, but interact similarly with MHC/peptide ligands (30).…”