Autoimmunity and tumor immunity induced by immune responses to mutations in self Journal Article
| Authors: | Engelhorn, M. E.; Guevara-Patiño, J. A.; Noffz, G.; Hooper, A. T.; Lou, O.; Gold, J. S.; Kappel, B. J.; Houghton, A. N. |
| Article Title: | Autoimmunity and tumor immunity induced by immune responses to mutations in self |
| Abstract: | Little is known about the consequences of immune recognition of mutated gene products, despite their potential relevance to autoimmunity and tumor immunity. To identify mutations that induce immunity, here we have developed a systematic approach in which combinatorial DNA libraries encoding large numbers of random mutations in two syngeneic tyrosinase-related proteins are used to immunize black mice. We show that the libraries of mutated DNA induce autoimmune hypopigmentation and tumor immunity through cross-recognition of nonmutated gene products. Truncations are present in all immunogenic clones and are sufficient to elicit immunity to self, triggering recognition of normally silent epitopes. Immunity is further enhanced by specific amino acid substitutions that promote T helper cell responses. Thus, presentation of a vast repertoire of antigen variants to the immune system can enhance the generation of adaptive immune responses to self. © 2006 Nature Publishing Group. |
| Keywords: | controlled study; gene mutation; mutation; nonhuman; cd8-positive t-lymphocytes; mouse; animals; mice; animal tissue; immune system; amino acid substitution; animal experiment; animal model; gene product; gene library; transfection; cercopithecus aethiops; cos cells; mice, inbred c57bl; animalia; immune response; amino acid sequence; molecular sequence data; antigens, neoplasm; immunogenicity; cd4-positive t-lymphocytes; recombinant proteins; epitope; neoplasms, experimental; autoantigens; tumor immunity; base sequence; autoimmunity; amino acid; mouse strain; complementary dna; helper cell; dna, complementary; hypopigmentation; immunization; self tolerance; intramolecular oxidoreductases; dna library; cross reactions; antigenic variation; combinatorial library |
| Journal Title: | Nature Medicine |
| Volume: | 12 |
| Issue: | 2 |
| ISSN: | 1078-8956 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2006-02-01 |
| Start Page: | 198 |
| End Page: | 206 |
| Language: | English |
| DOI: | 10.1038/nm1363 |
| PUBMED: | 16444264 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 47" - "Export Date: 4 June 2012" - "CODEN: NAMEF" - "Source: Scopus" |
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