Different development of myelin basic protein agonist- and antagonist-specific human TCR transgenic T cells in the thymus and periphery.
Myelin basic protein (MBP)-specific T cells are thought to play a role in the development of multiple sclerosis. MBP residues 111-129 compose an immunodominant epitope cluster restricted by HLA-DRB1*0401. The sequence of residues 111-129 of MBP (MBP(111-129)) differs in humans (MBP122:Arg) and mice (MBP122:Lys) at aa 122. We previously found that approximately 50% of human MBP(111-129) (MBP122:Arg)-specific T cell clones, including MS2-3C8 can proliferate in response to mouse MBP(111-129) (MBP122:Lys). However, the other half of T cell clones, including HD4-1C2, cannot proliferate in response to MBP(111-129) (MBP122:Lys). We found that MBP(111-129) (MBP122:Lys) is an antagonist for HD4-1C2 TCR, therefore, MS2-3C8 and HD4-1C2 TCRs are agonist- and antagonist-specific TCRs in mice, respectively. Therefore, we examined the development of HD4-1C2 TCR and MS2-3C8 TCR transgenic (Tg) T cells in the thymus and periphery. We found that dual TCR expression exclusively facilitates the development of MBP(111-129) TCR Tg T cells in the periphery of HD4-1C2 TCR/HLA-DRB1*0401 Tg mice although it is not required for their development in the thymus. We also found that MS2-3C8 TCR Tg CD8(+) T cells develop along with MS2-3C8 TCR Tg CD4(+) T cells, and that dual TCR expression was crucial for the development of MS2-3C8 TCR Tg CD4(+) and CD8(+) T cells in the thymus and periphery, respectively. These results suggest that thymic and peripheral development of MBP-specific T cells are different; however, dual TCR expression can facilitate their development.
Kawamura
Kazuyuki
K
Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, Bethesda, MD 20892, USA.
Yao
Karen
K
Shukaliak-Quandt
Jacqueline A
JA
Huh
Jaebong
J
Baig
Mirza
M
Quigley
Laura
L
Ito
Naoko
N
Necker
Antje
A
McFarland
Henry F
HF
Muraro
Paolo A
PA
Martin
Roland
R
Ito
Kouichi
K
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology*; D015870:Gene Expression / Q000235:genetics / Q000276:immunology; D006684:HLA-DR Antigens / Q000235:genetics / Q000276:immunology*; D059811:HLA-DRB1 Chains; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009103:Multiple Sclerosis / Q000235:genetics / Q000276:immunology*; D004676:Myelin Basic Protein; D009419:Nerve Tissue Proteins / Q000819:agonists* / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology; D010455:Peptides / Q000276:immunology / Q000494:pharmacology*; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology; D014157:Transcription Factors / Q000819:agonists* / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology
D018984:Epitopes, T-Lymphocyte; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; C553505:HLA-DRB1*04:01 antigen; C499048:MBP protein, human; C499047:Mbp protein, mouse; D004676:Myelin Basic Protein; D009419:Nerve Tissue Proteins; D010455:Peptides; D011948:Receptors, Antigen, T-Cell; D014157:Transcription Factors