Detection of autoreactive T cells in H-2u mice using peptide-MHC multimers.
Myelin basic protein (MBP)-specific T cells play a critical role in the pathogenesis of experimental autoimmune encephalomyelitis (EAE), a prototype for T cell-mediated autoimmunity. In PL/J and B10.PL mice (H-2(u) haplotype), the immunodominant epitope of MBP is represented by an N-terminal nonameric peptide, MBP1-9. To date, the MBP1-9-specific T cell repertoire has not been analyzed in quantitative terms. In the present study we demonstrate, using MHC class II tetramers, that 15,000-70,000 self-antigen-specific T(h) cells accumulate in the draining lymph nodes following immunization with spinal cord homogenate or MBP1-9. In contrast, MBP1-9-specific T cells are undetectable in unimmunized H-2(u) mice and represent >60% of the CD4 cells in naive mice transgenic for a TCR specific for this epitope. The results suggest that the extremely low affinity of the N-terminal peptide for I-A(u) does not limit the MBP1-9-specific T cells from expanding into a sizeable pool of autoreactive T cells. Therefore, the primary immune response to MBP1-9 does not differ quantitatively from previously reported CD4(+) T cell responses to foreign antigens.
Radu
C G
CG
Center for Immunology and Cancer Immunobiology Center, University of Texas Southwestern Medical Center, Dallas, TX 75235-8576, USA.
Anderton
S M
SM
Firan
M
M
Wraith
D C
DC
Ward
E S
ES
D000818:Animals; D001324:Autoantigens / Q000008:administration & dosage / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000096:biosynthesis / Q000276:immunology; D005620:Freund's Adjuvant / Q000276:immunology; D006183:H-2 Antigens / Q000096:biosynthesis / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis / Q000737:chemistry / Q000276:immunology*; D006825:Hybridomas; D007279:Injections, Subcutaneous; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D004676:Myelin Basic Protein / Q000008:administration & dosage / Q000276:immunology; D010446:Peptide Fragments / Q000008:administration & dosage / Q000096:biosynthesis / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000276:immunology*
D001324:Autoantigens; D018984:Epitopes, T-Lymphocyte; D006183:H-2 Antigens; D000949:Histocompatibility Antigens Class II; D004676:Myelin Basic Protein; D010446:Peptide Fragments; D016693:Receptors, Antigen, T-Cell, alpha-beta; C109168:T-cell receptor Vbeta 8.2; C074815:myelin basic protein 1-9; C405723:myelin basic protein Ac1-11(4Y); D005620:Freund's Adjuvant