Activation of murine epidermal V gamma 5/V delta 1-TCR(+) T cell lines by Glu-Tyr polypeptides.
The physiologic role of gamma delta-T-cell-receptor-bearing cells and the T cell receptor ligands that they recognize is still poorly understood. Previous studies have suggested that one possible antigen for gamma delta-TCR(+) cells is the random copolymer poly-glutamic acid-tyrosine (poly-Glu-Tyr), because poly-Glu-Tyr-reactive gamma delta-TCR(+) hybridoma cells were produced from poly-Glu-Tyr-immunized mice. We have found, however, that clonal V gamma 5/V delta 1-TCR(+) epidermal T cell lines from nonimmune mice also respond to poly-Glu-Tyr by producing cytokines. Other amino acid homopolymers, copolymers, and tripolymers were not stimulatory for the V gamma 5/V delta 1-TCR(+) epidermal T cells, except for poly-glutamic acid-alanine-tyrosine (poly-Glu-Ala-Tyr). Of the poly-Glu-Tyr and poly-Glu-Ala-Tyr polymers, only those that contained Glu and Tyr in an equimolar ratio were stimulatory. The cytokine interleukin-2 was strictly required for the responses to poly-Glu-Ala-Tyr, whereas the responses to poly-Glu-Tyr were merely enhanced with interleukin-2. The response to poly-Glu-Tyr was also enhanced by crosslinking CD28 molecules with plate-bound anti-CD28 crosslinking antibody. This finding suggests that the poly-Glu-Tyr response has a partial dependence on CD28-mediated costimulation, a characteristic of TCR-dependent responses. Consistent with this observation, V gamma 5/V delta 1-TCR-loss variants of the epidermal T cell line could no longer respond to poly-Glu-Tyr. The unpredicted responses of epidermal gamma delta-TCR(+) T cells to poly-Glu-Tyr and poly-Glu-Ala-Tyr demonstrate that the functions of these cells potentially can be triggered by peptidic ligands, probably through a TCR-mediated process.
Seo
S J
SJ
Department of Dermatology, Chung-Ang University, Pil-dong, Chung-ku, Seoul, South Korea.
Lahn
M
M
Cady
C
C
Vollmer
M
M
O'Brien
R L
RL
Born
W K
WK
Reardon
C L
CL
D018122:B7-1 Antigen / Q000502:physiology; D018106:CD28 Antigens / Q000502:physiology; D002460:Cell Line; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D007376:Interleukin-2 / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects*; D010455:Peptides / Q000494:pharmacology*; D011947:Receptors, Antigen, B-Cell / Q000502:physiology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis* / Q000502:physiology; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D018122:B7-1 Antigen; D018106:CD28 Antigens; D036341:Intercellular Signaling Peptides and Proteins; D007376:Interleukin-2; D010455:Peptides; D011947:Receptors, Antigen, B-Cell; D016692:Receptors, Antigen, T-Cell, gamma-delta; C027606:L-glutamic acid-L-tyrosine copolymer