Role of APC in the selection of immunodominant T cell epitopes

Chenglie Ma, Phyllis E. Whiteley, Patricia M. Cameron, Daniel C. Freed, Alison Pressey, Shiow Ling Chen, Beth Garni-Wagner, Carol Fang, Dennis M. Zaller, Linda S. Wicker, Janice S. Blum

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47 Scopus citations

Abstract

Following antigenic challenge, MHC-restricted T cell responses are directed against a few dominant antigenic epitopes. Here, evidence is provided demonstrating the importance of APC in modulating the hierarchy of MHC class II-restricted T cell responses. Biochemical analysis of class II:peptide complexes in B cells revealed the presentation of a hierarchy of peptides derived from the Ig self Ag. Functional studies of κ peptide:class II complexes from these cells indicated that nearly 20-fold more of an immunodominant epitope derived from κ L chains was bound to class II DR4 compared with a subdominant epitope from this same Ag. In vivo, T cell responses were preferentially directed against the dominant κ epitope as shown using Ig-primed DR4 transgenic mice. The bias in κ epitope presentation was not linked to differences in class II:κ peptide-binding affinity or epitope editing by HLA-DM. Rather, changes in native Ag structure were found to disrupt presentation of the immunodominant but not the subdominant κ epitope; Ag refolding restored κ epitope presentation. Thus, Ag tertiary conformation along with processing reactions within APC contribute to the selective presentation of a hierarchy of epitopes by MHC class II molecules.

Original languageEnglish (US)
Pages (from-to)6413-6423
Number of pages11
JournalJournal of Immunology
Volume163
Issue number12
StatePublished - Dec 28 1999

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Ma, C., Whiteley, P. E., Cameron, P. M., Freed, D. C., Pressey, A., Chen, S. L., Garni-Wagner, B., Fang, C., Zaller, D. M., Wicker, L. S., & Blum, J. S. (1999). Role of APC in the selection of immunodominant T cell epitopes. Journal of Immunology, 163(12), 6413-6423.