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 Blum

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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
Pages (from-to)6413-6423
Number of pages11
JournalJournal of Immunology
Volume163
Issue number12
StatePublished - 1999

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Immunodominant Epitopes
T-Lymphocyte Epitopes
Epitopes
Peptides
T-Lymphocytes
Transgenic Mice
B-Lymphocytes

ASJC Scopus subject areas

  • Immunology

Cite this

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

Role of APC in the selection of immunodominant T cell epitopes. / Ma, Chenglie; Whiteley, Phyllis E.; Cameron, Patricia M.; Freed, Daniel C.; Pressey, Alison; Chen, Shiow Ling; Garni-Wagner, Beth; Fang, Carol; Zaller, Dennis M.; Wicker, Linda S.; Blum, Janice.

In: Journal of Immunology, Vol. 163, No. 12, 1999, p. 6413-6423.

Research output: Contribution to journalArticle

Ma, C, Whiteley, PE, Cameron, PM, Freed, DC, Pressey, A, Chen, SL, Garni-Wagner, B, Fang, C, Zaller, DM, Wicker, LS & Blum, J 1999, 'Role of APC in the selection of immunodominant T cell epitopes', Journal of Immunology, vol. 163, no. 12, pp. 6413-6423.
Ma C, Whiteley PE, Cameron PM, Freed DC, Pressey A, Chen SL et al. Role of APC in the selection of immunodominant T cell epitopes. Journal of Immunology. 1999;163(12):6413-6423.
Ma, Chenglie ; Whiteley, Phyllis E. ; Cameron, Patricia M. ; Freed, Daniel C. ; Pressey, Alison ; Chen, Shiow Ling ; Garni-Wagner, Beth ; Fang, Carol ; Zaller, Dennis M. ; Wicker, Linda S. ; Blum, Janice. / Role of APC in the selection of immunodominant T cell epitopes. In: Journal of Immunology. 1999 ; Vol. 163, No. 12. pp. 6413-6423.
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