Evidence of a diverse T cell receptor repertoire for acetylcholine receptor, the autoantigen of myasthenia gravis.
We utilized two methods to look for T cell clonal expansions in myasthenia gravis (MG). We analyzed TCRBV CDR3 length polymorphism (spectratyping) to look for evidence of clonal expansion of CD4 or CD8 T cells directly from peripheral blood of MG patients. No statistically significant differences were found between the diversity of TCR repertoires in MG patients compared to normal control individuals when analyzed as groups. Rare oligoclonal expansions were detected in some individual MG patients but the significance of these findings is unclear. Next, we analyzed a panel of T cell hybridomas from acetylcholine receptor (AChR) immunized, MG-susceptible HLA-DR3 transgenic mice. The epitope specificity, TCRBV gene usage and CDR3 sequences of these hybridomas were highly diverse. We conclude there is only limited evidence for restricted TCR repertoire usage in human MG and suggest this may be due to the inability of HLA-DR molecules to select for restricted TCR recognition of AChR epitopes.
Infante
Anthony J
AJ
Department of Pediatrics, University of Texas Health Science Center, 7703 Floyd Curl Drive MC 7790, San Antonio, TX 78229-3900, USA. infantea@uthscsa.edu
Baillargeon
Jacques
J
Kraig
Ellen
E
Lott
Lisa
L
Jackson
Carlayne
C
Hämmerling
Gunter J
GJ
Raju
Raghavanpillai
R
David
Chella
C
D000328:Adult; D000368:Aged; D000818:Animals; D001324:Autoantigens / Q000276:immunology*; D018076:DNA, Complementary / Q000235:genetics; D004195:Disease Models, Animal; D000939:Epitopes / Q000276:immunology; D005260:Female; D015803:HLA-DR3 Antigen / Q000235:genetics / Q000276:immunology; D006801:Humans; D006825:Hybridomas / Q000276:immunology; D008297:Male; D051379:Mice; D008875:Middle Aged; D009157:Myasthenia Gravis / Q000097:blood / Q000235:genetics / Q000276:immunology*; D011110:Polymorphism, Genetic / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics* / Q000276:immunology*; D011950:Receptors, Cholinergic / Q000276:immunology*
D001324:Autoantigens; D018076:DNA, Complementary; D000939:Epitopes; D015803:HLA-DR3 Antigen; D016693:Receptors, Antigen, T-Cell, alpha-beta; D011950:Receptors, Cholinergic