Down-regulation of poison ivy/oak-induced contact sensitivity by treatment with a class II MHC binding peptide:hapten conjugate.
Immune regulation of contact sensitivity to the poison ivy/oak catechol was studied at the level of class II MHC-restricted T cell recognition of hapten:peptide conjugates. In this study we have shown that 1) T cells from C3H/HeN (H-2k) mice, immunized with a synthetic I-Ak binding peptide coupled to 3-pentadecyl-catechol (PDC; a representative catechol in urushiol), recognized peptides derived from syngeneic cells linked to the same catechol; 2) T cells from draining lymph nodes of C3H/HeN mice skin-painted with PDC proliferated in response to a peptide carrier:PDC conjugate only when it was linked at the 7th, but not the 4th or the 10th, position on the peptide carrier; and 3) tolerization studies confirmed down-regulation of PDC-induced delayed-type hypersensitivity following treatment with a single I-Ak binding peptide carrying PDC covalently bound to a lysine residue at the middle (7th) TCR contact position. Tolerization with peptide:PDC conjugate resulted in abrogation of hapten-specific T cell proliferative responses that correlated with diminished IL-2 secretion. On the basis of these data we propose that it may be sufficient to couple the hapten at a single, well-chosen position on a carrier peptide to target a relevant population of T cells involved in contact sensitivity.
Gelber
C
C
ImmuLogic Pharmaceutical Corporation, Waltham, MA 02154, USA.
Gemmell
L
L
McAteer
D
D
Homola
M
M
Swain
P
P
Liu
A
A
Wilson
K J
KJ
Gefter
M
M
D000287:Administration, Topical; D000818:Animals; D002352:Carrier Proteins / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use*; D002396:Catechols / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry; D011040:Dermatitis, Toxicodendron / Q000276:immunology* / Q000517:prevention & control; D015536:Down-Regulation / Q000276:immunology*; D006241:Haptens / Q000276:immunology / Q000627:therapeutic use*; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D007108:Immune Tolerance / Q000187:drug effects; D007376:Interleukin-2 / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008805:Mice, Inbred A; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D010455:Peptides / Q000378:metabolism / Q000502:physiology; D011485:Protein Binding / Q000187:drug effects / Q000276:immunology; D012867:Skin / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D014301:Trinitrobenzenes / Q000276:immunology / Q000627:therapeutic use*
D002352:Carrier Proteins; D002396:Catechols; D006241:Haptens; D000949:Histocompatibility Antigens Class II; D007376:Interleukin-2; D010455:Peptides; D014301:Trinitrobenzenes; C005297:3-pentadecacatechol