T-Cell Receptor Vα and Cα Alleles Associated with Multiple Sclerosis and Myasthenia Gravis

• Published in: Proceedings of the National Academy of Sciences - PNAS 1989-02, Vol.86 (3), p.988-992
• Main Authors: Oksenberg, Jorge R., Sherritt, Martina, Begovich, Ann B., Erlich, Henry A., Bernard, Claude C., Cavalli-Sforza, Luigi L., Steinman, Lawrence
• Format: Article
• Language: English
• Subjects: Autoimmune diseases; Autoimmunity (experimental aspects and models); Biological and medical sciences; Complementary DNA; DNA; DNA probes; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Medical genetics; Multiple sclerosis; Myasthenia gravis; Nervous system diseases; Phenotypes; Polymerase chain reaction
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.86.3.988

Polymorphic markers in genes encoding the α chain of the human T-cell receptor (TcR) have been detected by Southern blot analysis in Pss I digests. Polymorphic bands were observed at 6.3 and 2.0 kilobases (kb) with frequencies of 0.30 and 0.44, respectively, in the general population. Using the polymerase chain reaction (PCR) method, we amplified selected sequences derived from the full-length TcR α cDNA probe. These PCR products were used as specific probes to demonstrate that the 6.3-kb polymorphic fragment hybridizes to the variable (V)-region probe and the 2.0-kb fragment hybridizes to the constant (C)-region probe. Segregation of the polymorphic bands was analyzed in family studies. To look for associations between these markers and autoimmune diseases, we have studied the restriction fragment length polymorphism distribution of the Pss I markers in patients with multiple sclerosis, myasthenia gravis, and Graves disease. Significant differences in the frequency of the polymorphic Vα and Cα markers were identified between patients and healthy individuals.