Limited repertoire of HLA-DRB1*0401-restricted MBP111-129-specific T cells in HLA-DRB1*0401 Tg mice and their pathogenic potential.
Since myelin basic protein (MBP)111-129 is an immunodominant epitope in humans carrying HLA-DRB1*0401, we investigated the encephalitogenic potential of HLA-DRB1*0401-restricted MBP111-129-specific T cells using HLA-DRB1*0401/DRA*0101 transgenic (Tg) mice. Although we could not detect the primary recall response to MBP111-129 peptide after immunization of HLA-DRB1*0401/DRA*0101 Tg mice with human MBP, V beta 10(+) and V beta 2(+) HLA-DRB1*0401-restricted MBP111-129-specific T cells proliferated after restimulation of the lymph node cells with human MBP111-129 in vitro. The V beta 2(+) T cell line recognized only human MBP111-129 in the context of HLA-DRB1*0401, while the V beta 10(+) T cell line recognized both the human and murine MBP111-129 epitopes. Therefore, we examined the encephalitogenic potential of the V beta 10(+) T cell line in HLA-DRB1*0401/DRA*0101 Tg mice by adoptive transfer experiments. The V beta 10(+) T cell line induced mild EAE and inflammatory lesions were observed in the spinal cord and the brainstem. In the spinal cord, the inflammation was observed in the peripheral nerve roots as well as in the CNS. These data suggest the pathogenic potential of HLA-DRB1*0401-restricted MBP111-129-specific T cells in humans.
Huh
Jaebong
J
Neuroimmunology Branch, National Institute of Neurological Diseases and Stroke, National Institutes of Health, 10-5B16, 10 Center Drive, Bethesda, MD 20892, USA.
Yao
Karen
K
Quigley
Laura
L
Ludwin
Samuel K
SK
McFarland
Henry F
HF
Muraro
Paolo A
PA
Martin
Roland
R
Ito
Kouichi
K
D019264:Adoptive Transfer; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002490:Central Nervous System / Q000276:immunology / Q000473:pathology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte; D005434:Flow Cytometry; D006684:HLA-DR Antigens / Q000276:immunology*; D059811:HLA-DRB1 Chains; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D004676:Myelin Basic Protein / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D018984:Epitopes, T-Lymphocyte; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; C553505:HLA-DRB1*04:01 antigen; D004676:Myelin Basic Protein; D010446:Peptide Fragments; D016693:Receptors, Antigen, T-Cell, alpha-beta