T cell receptor beta chain gene rearrangement shared by murine T cell lines derived from a site of autoimmune inflammation.
Advances in our understanding of the structure and molecular biology of the T lymphocyte antigen-receptor have now made it feasible to study human autoimmune diseases using new approaches. One such approach involves cloning of T cells from sites of autoimmune pathology followed by identification of putative disease-related T cell oligoclonality at the level of the T cell receptor gene rearrangements. We have now tested the feasibility of this approach in an animal model of autoimmunity, murine experimental allergic encephalomyelitis (EAE). Spinal cord-derived, self (murine) myelin basic protein (MBP)-reactive T cell lines and sublines were analyzed at the level of their receptor beta chain rearrangements using Southern blots. We now report that the MBP-reactive T cell lines and sublines derived from the spinal cords of four of five SJL/J mice with EAE share a 14.5-kb rearranged T cell receptor beta 1 band on Southern blots. A spinal cord-derived T cell line that was reactive to purified protein derivative of tuberculin (PPD), several lymph node-derived ovalbumin- and PPD-reactive T cell lines, as well as one MBP-reactive spinal cord-derived T cell line did not share this 14.5-kb rearranged beta 1 band. These results suggest that analysis of the antigen receptors used by T cells cloned from sites of inflammation may be a useful initial approach for identifying pathogenetically relevant T cells in the study of certain human autoimmune diseases.
Padula
S J
SJ
Department of Medicine, University of Connecticut School of Medicine, Farmington 06032.
Sgroi
D C
DC
Lingenheld
E G
EG
Love
J T
JT
Chou
C H
CH
Clark
R B
RB
D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology*; D001345:Autoradiography; D002460:Cell Line; D003001:Cloning, Molecular; D004247:DNA / Q000032:analysis; D004262:DNA Restriction Enzymes; D015247:Deoxyribonuclease HindIII; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology*; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D004676:Myelin Basic Protein / Q000276:immunology; D009693:Nucleic Acid Hybridization; D010047:Ovalbumin / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D013116:Spinal Cord / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D014373:Tuberculin / Q000276:immunology
D004676:Myelin Basic Protein; D011948:Receptors, Antigen, T-Cell; D014373:Tuberculin; D010047:Ovalbumin; D004247:DNA; D004262:DNA Restriction Enzymes; D015247:Deoxyribonuclease HindIII