Decrypting the spectrum of antigen-specific T-cell responses: The avidity repertoire of MBP-specific T-cells

B. Mazzanti, B. Hemmer, E. Traggiai, C. Ballerini, H. F. McFarland, L. Massacesi, R. Martin, Marco Vergelli

Research output: Contribution to journalArticlepeer-review

Abstract

Myelin basic protein (MBP) is a well-characterized autoantigen potentially involved in the pathogenesis of the most common human demyelinating disease of the central nervous system (CNS), multiple sclerosis (MS). It is known that MBP-specific T-cell responses differ widely among different individuals and also within a single donor in terms of fine specificity and functional characteristics including the avidity in antigen recognition. In this report, we demonstrate that the in vitro selection of MBP-reactive T-cell repertoire is strictly dependent upon the antigen dose used in the primary cultures. MBP-specific T-cell lines (TCLs) were generated from MS patients and healthy donors using different antigen concentration in cultures (0.1 to 50 μg/ml). In both MS patients and controls, the number of obtained T-cell lines was affected by the antigen concentration. In addition, low and high antigen concentrations selected in vitro different T-cell populations in terms of peptide specificity patterns and different functional avidities in antigen recognition. Low concentrations of MBP in the primary cultures yielded a small number of TCLs recognizing the specific antigen with higher avidity whereas high antigen concentrations allowed the in vitro expansion of a higher numbers of T-cells recognizing MBP with lower avidity. The use of different antigen concentrations in the primary cultures can be applied as a simple experimental system to investigate the overall avidity repertoire of antigen-specific T-cell response in humans.

Original languageEnglish (US)
Pages (from-to)86-93
Number of pages8
JournalJournal of Neuroscience Research
Volume59
Issue number1
DOIs
StatePublished - Jan 1 2000
Externally publishedYes

Keywords

  • Antigen concentration
  • Multiple sclerosis
  • Myelin basic protein
  • T-cell response

ASJC Scopus subject areas

  • Neuroscience(all)

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