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Inhibition of an In Vitro CD4⁺ T Cell Alloresponse Using Altered Peptide Ligands¹

Department of Pathology and Center for Immunology, Washington University School of Medicine, St. Louis, MO 63110

In this study, we explore the potential of altered peptide ligands (APLs) to modulate the alloresponse of CD4⁺ T cells using elements of the murine hemoglobin (Hb) Ag model. We first demonstrated that the T cell 2.102, specific for the Hb(64-76)/I-E^k complex, was alloreactive against splenocytes of the H-2^p haplotype. Using Ab-blocking and transfection experiments, we further showed that this alloreactivity was restricted to the class II molecule I-E^p. We tested a panel of APLs previously shown to antagonize the Hb response of 2.102 and found that these peptides could also effectively inhibit the alloresponse to I-E^p. Importantly, these peptides were able to antagonize the alloresponse of naive T cells derived from mice transgenic for the 2.102 TCR, as well as Th1 and Th2 cell lines. The antagonism required the presence of both I-E^p and I-E^k on the same APC. Our study demonstrates the effectiveness of APLs to antagonize the primary alloresponse of specific T cells and provides a basis for the development of immunotherapeutics for use in transplantation and immune-mediated diseases.

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