An essential role for constitutive Schiff base-forming ligands in antigen presentation to murine T cell clones.
The role of cell-surface Schiff base-forming ligands in the inductive interaction between class II+ APC and murine T cells was investigated. Schiff bases are produced by the condensation of an amine with the carbonyl group of an aldehyde or ketone in a reversible covalent reaction. Treatment of APC with low concentrations of glutaraldehyde to form Schiff bases on a small proportion of epsilon-amino groups consistently inhibited Ag presentation to primary T cells and T cell clones. Schiff base formation by glutaraldehyde was quantitated by specific reduction with the weak, selective reducing agent sodium cyanoborohydride. Aldehyde inhibition of presentation was observed with allo-, protein, and small peptide Ag, and T cell clones of Th1 and Th2 subtypes were equally susceptible. Large increases in the concentration of glutaraldehyde in brief pretreatments of APC resulted in substantial restoration of Ag-presenting function. Oxidation of T cell sialic acid to produce cell-surface aldehydes resulted in a vigorous proliferative response to class II-positive syngeneic accessory cells. This response was inhibited by preformation of Schiff bases on epsilon-amino groups of the accessory cells by glutaraldehyde. Dose response curves for inhibition of aldehyde-induced and Ag-induced T cell proliferation by glutaraldehyde treatment of accessory cells were similar. Reduction of constitutive aldehydes on cloned T cells by sodium borohydride resulted in inhibition of Ag-specific responses. This took the form of a substantial delay in the time-course of the response consistent with the eventual regeneration of cell-surface aldehydes. Only the presentation of Ag was inhibited. Ongoing established proliferative responses remained unaffected. Together, these data indicate that constitutive Schiff base-forming ligands on APC and T cells are essential in Ag presentation to murine T cells and are consistent with a model of Ag presentation in which reciprocal Schiff base formation is an essential element.
Gao
X M
XM
Department of Experimental Immunobiology, Wellcome Biotech, Beckenham, Kent, UK.
Rhodes
J
J
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D001894:Borohydrides / Q000494:pharmacology; D055598:Chemical Phenomena; D002621:Chemistry; D002999:Clone Cells; D005976:Glutaral; D007371:Interferon-gamma / Q000494:pharmacology; D008024:Ligands; D008213:Lymphocyte Activation; D008264:Macrophages / Q000502:physiology; D051379:Mice; D008815:Mice, Inbred Strains; D012545:Schiff Bases; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
D001894:Borohydrides; D008024:Ligands; D012545:Schiff Bases; D007371:Interferon-gamma; C025364:sodium borohydride; D005976:Glutaral