Susceptible MHC alleles, not background genes, select an autoimmune T cell reactivity.
To detect and characterize autoreactive T cells in diabetes-prone NOD mice, we have developed a multimeric MHC reagent with high affinity for the BDC-2.5 T cell receptor, which is reactive against a pancreatic autoantigen. A distinct population of T cells is detected in NOD mice that recognizes the same MHC/peptide target. These T cells are positively selected in the thymus at a surprisingly high frequency and exported to the periphery. They are activated specifically in the pancreatic LNs, demonstrating an autoimmune specificity that recapitulates that of the BDC-2.5 cell. These phenomena are also observed in mouse lines that share with NOD the H-2g7 MHC haplotype but carry diabetes-resistance background genes. Thus, a susceptible haplotype at the MHC seems to be the only element required for the selection and emergence of autoreactive T cells, without requiring other diabetogenic loci from the NOD genome.
Stratmann
Thomas
T
Department of Immunology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
Martin-Orozco
Natalia
N
Mallet-Designe
Valérie
V
Poirot
Laurent
L
McGavern
Dorian
D
Losyev
Grigoriy
G
Dobbs
Cathleen M
CM
Oldstone
Michael B A
MB
Yoshida
Kenji
K
Kikutani
Hitoshi
H
Mathis
Diane
D
Benoist
Christophe
C
Haskins
Kathryn
K
Teyton
Luc
L
D000483:Alleles; D000818:Animals; D001324:Autoantigens / Q000276:immunology; D015551:Autoimmunity; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000502:physiology; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000378:metabolism; D005260:Female; D006239:Haplotypes; D006825:Hybridomas / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008285:Major Histocompatibility Complex / Q000235:genetics*; D051379:Mice; D016688:Mice, Inbred NOD; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000378:metabolism
D001324:Autoantigens; D011948:Receptors, Antigen, T-Cell