Altered TCR ligands affect antigen-presenting cell responses: up-regulation of IL-12 by an analogue peptide.
When examining the effects of analogue peptides on changes in response patterns of a human Th0 clone DT13.2 that recognizes a peptide fragment (18RSLRTVTPIRMQGG31) derived from a group I allergen in Dermatophagoides farinae in the context of HLA-DQ6 (DQA1*0102/DQB1*0602), we found that replacement of the 21st residue Arg to Lys resulted in a significant increase in IFN-gamma production, with no remarkable changes either in proliferative response or IL-4 production, at high doses of the peptide. Selective enhancement of IFN-gamma production by the analogue peptide was accompanied by an increased production of IL-12, which was suppressed by an anti-IL-12 Ab down to the level of IFN-gamma production induced by the wild-type peptide. On the contrary, co-incubation with neutralizing Abs to IFN-gamma and IFN-gamma receptor did not affect IL-12 production, indicating that increased production of IL-12 stimulated by the analogue peptide was not due to an effect of IFN-gamma from T cells. Peptide-induced up-regulation of CD40 ligand expression at high peptide concentrations showed no difference between the wild-type and analogue peptides. These data collectively indicate that certain T cell/APC interactions mediated through TCR and altered TCR ligands affect APC responses and that signals transmitted to APC are as indispensable as those to T cells in determining T cell response patterns.
Matsuoka
T
T
Department of Neuroscience and Immunology, Kumamoto University Graduate School of Medical Sciences, Japan.
Kohrogi
H
H
Ando
M
M
Nishimura
Y
Y
Matsushita
S
S
D000485:Allergens / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D015703:Antigens, CD / Q000378:metabolism; D039741:Antigens, Dermatophagoides; D023201:CD40 Ligand; D002999:Clone Cells; D006023:Glycoproteins / Q000235:genetics / Q000276:immunology; D006680:HLA Antigens; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis*; D008024:Ligands; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000378:metabolism; D008925:Mites / Q000235:genetics / Q000276:immunology; D009500:Neutralization Tests; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology; D010455:Peptides / Q000235:genetics / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D017471:Receptors, Interferon / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology; D015854:Up-Regulation; D000096743:Interferon gamma Receptor
D000485:Allergens; D015703:Antigens, CD; D039741:Antigens, Dermatophagoides; D023201:CD40 Ligand; D006023:Glycoproteins; D006680:HLA Antigens; D007371:Interferon-gamma; D018664:Interleukin-12; D008024:Ligands; D008562:Membrane Glycoproteins; D010446:Peptide Fragments; D010455:Peptides; D011948:Receptors, Antigen, T-Cell; D017471:Receptors, Interferon; D000096743:Interferon gamma Receptor