Structural requirements for peptides that stimulate a subset of γδ T cells

Yang Xin Fu, Michaelann Vollmer, Harshan Kalataradi, Kent Heyborne, Christopher Reardon, Craig Miles, Rebecca O'Brien, Willi Born

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44 Scopus citations


Hybridomas representing the Vγ1-positive subset of murine γδ T cells secrete lymphokines in response to synthetic peptides representing a short segment of the mycobacterial 60-kDa heat shock protein (HSP-60). Here we show the TCR dependency of this response by transfection of productively rearranged TCR genes derived from an HSP-60 reactive γδ T cell hybridoma. We also have defined structural requirements for the stimulatory peptide. The smallest HSP-60 peptide capable of stimulating these hybridomas is seven amino acids long, representing positions 181-187, and having the sequence FGLQLEL. Amino acid-substituted derivatives of this peptide, and another containing the same core, p180-190, revealed amino acids essential for stimulatory activity. Phenylalanine in position 181 and leucine in position 183 seem to be required for stimulation of all HSP-60 reactive cells, whereas others are only required by some. Clonal differences in the responses to these peptides provide indirect evidence for cognate TCR-peptide interactions. The smallest stimulatory peptide, p181-187, represents an area not well conserved among HSP-60 molecules of other species, and stimulates a mycobacteria-specific response unlike the earlier observed cross-reactive responses of the same hybridomas with longer HSP-60 peptides derived from mycobacteria and other species (our manuscript in preparation). We propose that the TCR-dependent multiclonal γδ T cell response to HSP-60 peptides and derivatives, which in some ways resembles superantigen responses and in other ways resembles responses to conventional Ag, may be a separate, third type of Ag response by T cells.

Original languageEnglish (US)
Pages (from-to)1578-1588
Number of pages11
JournalJournal of Immunology
Issue number4
StatePublished - Feb 15 1994

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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