Structural requirements for peptides that stimulate a subset of gamma delta T cells.
Hybridomas representing the V gamma 1-positive subset of murine gamma delta 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 gamma delta 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 gamma delta 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.
Fu
Y X
YX
Department of Medicine, National Jewish Center for Immunology and Respiratory Medicine, Denver, CO 80206.
Vollmer
M
M
Kalataradi
H
H
Heyborne
K
K
Reardon
C
C
Miles
C
C
O'Brien
R
R
Born
W
W
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D006360:Heat-Shock Proteins / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis*; D013329:Structure-Activity Relationship; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D006360:Heat-Shock Proteins; D010446:Peptide Fragments; D016692:Receptors, Antigen, T-Cell, gamma-delta