Peptide ligand structure and I-Aq binding avidity influence T cell signaling pathway utilization

Linda Myers, David L. Cullins, Jeoung Eun Park, Ae-Kyung Yi, David Brand, Edward F. Rosloniec, John Stuart, Andrew Kang

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Factors that drive T cells to signal through differing pathways remain unclear. We have shown that an altered peptide ligand (A9) activates T cells to utilize an alternate signaling pathway which is dependent upon FcRγ and Syk. However, it remains unknown whether the affinity of peptide binding to MHC drives this selection. To answer this question we developed a panel of peptides designed so that amino acids interacting with the p6 and p9 predicted MHC binding pockets were altered. Analogs were tested for binding to I-Aq using a competitive binding assay and selected analogs were administered to arthritic mice. Using the collagen-induced arthritis (CIA) model, arthritis severity was correlated with T cell cytokine production and molecular T cell signaling responses. We establish that reduced affinity of interaction with the MHC correlates with T cell signaling through the alternative pathway, leading ultimately to secretion of suppressive cytokines and attenuation of arthritis.

Original languageEnglish (US)
Pages (from-to)188-197
Number of pages10
JournalClinical Immunology
Volume160
Issue number2
DOIs
StatePublished - Oct 1 2015

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Ligands
Arthritis
T-Lymphocytes
Peptides
Cytokines
TCF Transcription Factors
Experimental Arthritis
Competitive Binding
Amino Acids
MHC binding peptide

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Peptide ligand structure and I-Aq binding avidity influence T cell signaling pathway utilization. / Myers, Linda; Cullins, David L.; Park, Jeoung Eun; Yi, Ae-Kyung; Brand, David; Rosloniec, Edward F.; Stuart, John; Kang, Andrew.

In: Clinical Immunology, Vol. 160, No. 2, 01.10.2015, p. 188-197.

Research output: Contribution to journalArticle

Myers, Linda ; Cullins, David L. ; Park, Jeoung Eun ; Yi, Ae-Kyung ; Brand, David ; Rosloniec, Edward F. ; Stuart, John ; Kang, Andrew. / Peptide ligand structure and I-Aq binding avidity influence T cell signaling pathway utilization. In: Clinical Immunology. 2015 ; Vol. 160, No. 2. pp. 188-197.
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