Identification of a cross‐reactive self ligand in virus‐mediated autoimmunity

• Published in: European journal of immunology Vol. 29; no. 9; pp. 2886 - 2896
• Main Authors: Ohteki, Toshiaki, Hessel, Andrew, Bachmann, Martin F., Zakarian, Arsen, Sebzda, Eric, Tsao, Ming S., McKall‐Faienza, Kim, Odermatt, Bernhard, Ohashi, Pamela S.
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY‐VCH Verlag GmbH 01-09-1999
• Subjects: Allergens - immunology; Animals; Autoimmunity; Autoimmunity - immunology; Cross Reactions; DNA-Binding Proteins; Epitopes - immunology; Epitopes - isolation & purification; H-2 Antigens - analysis; H-2 Antigens - immunology; Ligands; Lymphocytic choriomeningitis virus; Lymphocytic choriomeningitis virus - immunology; Mice; Mice, Congenic; Mice, Inbred C57BL - immunology; Mice, Transgenic; Molecular mimicry; Molecular Mimicry - immunology; Peptide; Receptors, Antigen, T-Cell - agonists; Receptors, Antigen, T-Cell - antagonists & inhibitors; Receptors, Antigen, T-Cell - genetics; Receptors, Antigen, T-Cell - immunology; TCR flexibility; Tumor Cells, Cultured
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/(SICI)1521-4141(199909)29:09<2886::AID-IMMU2886>3.0.CO;2-A

Molecular mimicry has been considered to be one of the potential mechanisms underlying the induction of autoimmune diseases. Using a TCR‐transgenic model specific for lymphocytic choriomeningitis virus (LCMV) we have examined the potential for cross‐reactive recognition of tissue‐restricted self peptides. Several peptides were identified that were able to cross‐react with the TCR‐transgenic virus‐specific T cells in vitro. One peptide was derived from dopamine β‐mono‐oxygenase, an enzyme expressed in the adrenal medulla. Interestingly, after activation of the transgenic T cells with LCMV glycoprotein peptides or viruses, infiltration of the adrenal medulla was detected in conjunction with alterations in dopamine metabolism. However, complete destruction of the adrenal medulla was not observed. This suggests that molecular mimicry may be sufficient for self recognition and infiltration, but other factors clearly contribute to chronic autoimmune disease.