The myelin basic protein-specific T cell repertoire in Lewis rats: T cell receptor diversity is influenced both by intrathymic milieu and by extrathymic peptide presentation.
In the Lewis rat, the T lymphocyte response to guinea pig myelin basic protein (MBP) is focused almost exclusively on epitopes nested in the MBP peptide sequence p68-88, and is dominated by T cell receptors (TCR) using Vbeta8.2 gene elements, together with short N(D)N regions. Here we analyzed MBP-specific TCR from Lewis T cells differentiating in chimeric thymuses of Lewis rat/SCID mouse chimeras, in the absence of an intact rat thymic microenvironment (SCID(FL) mice). In these T cells, the TCR Vbeta repertoire is broad, N(D)N regions are significantly longer, and contain regular rates of template-independent N nucleotides. In striking contrast, a Vbeta8.2 biased TCR repertoire and few N-region inserts are seen in p68-88-specific, Lewis rat-derived T cells differentiating in the complete rat thymic microenvironment provided by chimeric SCID mice bearing embryonic Lewis thymus grafts (SCID(FL/FT) mice). A T cell repertoire resembling the one in SCID(FL) mice is used by T cells of intact Lewis rats following immunization with a truncated epitope of MBP, p69-86. Also this selection generates a broad TCR Vbeta pattern with long N(D)N regions, and higher numbers of N nucleotides. These results show that both intrathymic repertoire selection, and extrathymic peptide priming exert profound effects on the TCR usage in the anti-MBP response of Lewis rats.
Kääb
G
G
Max-Planck-Institute for Neurobiology, Martinsried, Germany.
Haarmann
I
I
Wekerle
H
H
Bradl
M
M
D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation / Q000235:genetics; D001483:Base Sequence; D002469:Cell Separation; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015329:Gene Rearrangement, T-Lymphocyte; D006168:Guinea Pigs; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D016513:Mice, SCID; D008969:Molecular Sequence Data; D005810:Multigene Family / Q000276:immunology; D004676:Myelin Basic Protein / Q000276:immunology* / Q000378:metabolism; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000276:immunology / Q000378:metabolism; D013950:Thymus Gland / Q000196:embryology / Q000378:metabolism* / Q000637:transplantation
D018984:Epitopes, T-Lymphocyte; D004676:Myelin Basic Protein; D010446:Peptide Fragments; D016693:Receptors, Antigen, T-Cell, alpha-beta; D011993:Recombinant Fusion Proteins; C079716:myelin basic protein 68-88