Human and murine CD4 T cell reactivity to a complex antigen: Recognition of the synthetic random polypeptide glatiramer acetate

P. W. Duda, J. I. Krieger, M. C. Schmied, C. Balentine, D. A. Hafler

Research output: Contribution to journalArticlepeer-review

58 Scopus citations

Abstract

The capacity of glatiramer acetate (GA), a random copolymer of alanine, lysine, glutamic acid, and tyrosine to stimulate primary in vitro human and murine T cell proliferation was examined. PBMCs isolated from healthy humans and relapsing remitting multiple sclerosis patients and spleen cells from inbred strains of mice, expressing different II-2 haplotypes, were used as sources of non-GA-primed lymphocytes. GA functioned as a universal Ag, inducing dose-dependent proliferation of all non-GA-primed human and murine T cell populations tested. Moreover, GA stimulated PBMCs derived ex vivo from human cord blood, strongly suggesting that GA can activate both naive and memory T cells. The human T cell proliferative responses to GA were HLA class II DR-restricted by virtue of the ability of anti-class II Ab to inhibit T cell proliferation, and the demonstration that individual GA specific human T cell clones were HLA class II DR-restricted by either restriction element but not both. Furthermore, GA-reactive T cells secreted Th0 cytokines and expressed a diverse repertoire of TCR. Limiting dilution analysis indicated that the T cell precursor frequency among the healthy human adults tested ranged from 1:5,000 to 1:125,000. Given that all of the T cell populations tested were isolated from non-GA-primed donors, it appears that virtually all humans and murine strains contain significant numbers of T cell populations cross-reactive with GA. These findings may explain the recent clinical finding that daily s.c. administration of GA ameliorates the progression of multiple sclerosis.

Original languageEnglish (US)
Pages (from-to)7300-7307
Number of pages8
JournalJournal of Immunology
Volume165
Issue number12
DOIs
StatePublished - Dec 15 2000

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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