title: Structure-immune response relationships of hapten-modified collagen II peptides in a T-cell model of allergic contact dermatitis.
abstract: Allergic contact dermatitis (ACD) is mediated by T cells that specifically recognize hapten-modified peptides. T cells are known to recognize antigens as short processed peptides bound to major histocompatibility complex (MHC) molecules on the surface of antigen-presenting cells (APC). It has previously been demonstrated that T cells can specifically recognize carbohydrates on the lysine at position 264 of the immunodominant (256-273) sequence from type II collagen (CII) and that such recognition is critical for the development of arthritis in mice and may play a role in rheumatoid arthritis in humans. In the present study, we have used this approach in modeling ACD, but instead of the carbohydrate, the strong sensitizer 2,4-dinitrofluorobenzene (DNFB) is bound to the epsilon-amine of the lysine at position 264. Specific T-cell hybridomas of this antigenic peptide, with dinitrophenyl (Dnp) on the epsilon-amine of lysine at position 264 (CIILysDnp 3), were established from mice immunized with CIILysDnp 3. In an immune response assay, these T-cell hybridomas were tested with a series of new synthetic hapten-modified peptides, all chemically identical except for the stereochemimistry (D, L) and the length of the position-264 amino acid side chain bonding the hapten. The T-cell hybridomas recognized the CIILysDnp 3 peptide used for immunization; interestingly, they also recognized the CII peptide with a one-carbon-longer side chain (homolysine), CIIhLysDnp 6, and CIIAlaPipDnp 11, having a ring structure analogous to that of lysine with the same number of carbons in the bonding chain as in the CIILysDnp 3 peptide used for immunization. Dnp-modified CII peptides with a shorter bonding chain produced no immune response. These data demonstrate that the T-cell recognition of the Dnp-modified peptides is highly specific and moreover dependent on the length of the amino acid side chain that bonds the Dnp.
authors.affiliation: Department of Dermatology, Lund University Hospital, SE-221 85 Lund, Sweden.
authors.forename: Meirav
authors.initials: M
authors.lastname: Holmdahl
authors.forename: Stefan R
authors.initials: SR
authors.lastname: Ahlfors
authors.forename: Rikard
authors.initials: R
authors.lastname: Holmdahl
authors.forename: Christer
authors.initials: C
authors.lastname: Hansson
mesh_terms: D000818:Animals; D024043:Collagen Type II / Q000276:immunology* / Q000378:metabolism; D003429:Cross Reactions / Q000276:immunology; D017449:Dermatitis, Allergic Contact / Q000276:immunology* / Q000378:metabolism; D004139:Dinitrofluorobenzene / Q000276:immunology / Q000378:metabolism; D006241:Haptens / Q000276:immunology / Q000378:metabolism; D006825:Hybridomas; D016056:Immunodominant Epitopes / Q000276:immunology / Q000378:metabolism; D008239:Lysine / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D010455:Peptides / Q000276:immunology* / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000378:metabolism; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
chemical_list: D024043:Collagen Type II; D006241:Haptens; D016056:Immunodominant Epitopes; D010455:Peptides; D011948:Receptors, Antigen, T-Cell; D004139:Dinitrofluorobenzene; D008239:Lysine