TY - JOUR
T1 - Inhibition of an in vitro CD4+ T cells alloresponse using altered peptide ligands
AU - Daniel, Claude
AU - Grakoui, Arash
AU - Allen, Paul M.
PY - 1998/4/1
Y1 - 1998/4/1
N2 - 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 peptide were able to antogonize the alloresponse to 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.
AB - 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 peptide were able to antogonize the alloresponse to 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.
UR - http://www.scopus.com/inward/record.url?scp=0032055548&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.160.7.3244
DO - 10.4049/jimmunol.160.7.3244
M3 - Article
C2 - 9531280
AN - SCOPUS:0032055548
SN - 0022-1767
VL - 160
SP - 3244
EP - 3250
JO - Journal of Immunology
JF - Journal of Immunology
IS - 7
ER -