Auto-delayed-type hypersensitivity induced in immunodeficient mice with modified self-antigens. V. Cellular autoreactivity directed against self-H-2Dd subregion mediates the inflammatory responses.
X-irradiated (250 rads) A mice injected with syngeneic trinitrophenylated spleen cells (Syn-TNP-SC) developed syngeneic delayed-type hypersensitivity (Syn-DTH) after footpad challenge with syngeneic concanavalin A-induced lymphoblasts (Syn-Con A blasts), as indicated by footpad swelling and lymph-node proliferation assays. Genetic analysis with different recombinant strains of mouse revealed that the H-2Dd subregion restricts these immunological activities. A small immunogenic entity was isolated from Syn-TNP-SC extract by gel filtration and affinity chromatography with anti-Dd antibody. X-irradiated A mice injected with this antigen also generated inflammatory responses after challenge with Syn-Con A blasts. Analysis of the data obtained from the gel filtration and the affinity chromatography suggest that the Syn-DTH-stimulating antigen is a fragment of the H-2Dd heavy chain with a molecular weight (MW) of 5,000 to 10,000. This fragment does not contain TNP molecules or sugar moieties and neither does it express affinity for antibodies against class II products. Ltk-cells transfected with the H-2Dd gene also induced Syn-DTH in X-irradiated A mice, while the parent cells failed to stimulate such a response. Taken together these findings indicate that the selection process in the thymus is not absolute and T cells recognizing self-major histocompatibility complex (MHC) products do migrate from this organ to the periphery of the immune system. The possible biological significance of these autoreactive cells is discussed.
Tarcic
N
N
Lautenberg Center for General and Tumor Immunology, Hebrew University, Jerusalem, Israel.
David
C S
CS
Naor
D
D
D000818:Animals; D001324:Autoantigens / Q000235:genetics / Q000276:immunology*; D005260:Female; D005802:Genes, MHC Class II; D006183:H-2 Antigens / Q000235:genetics / Q000276:immunology*; D006968:Hypersensitivity, Delayed / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D007153:Immunologic Deficiency Syndromes / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D051379:Mice; D008805:Mice, Inbred A; D008807:Mice, Inbred BALB C; D008817:Mice, Mutant Strains; D013154:Spleen; D013601:T-Lymphocytes / Q000276:immunology; D014162:Transfection; D014301:Trinitrobenzenes
D001324:Autoantigens; D006183:H-2 Antigens; D014301:Trinitrobenzenes