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 Vβ8.2 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 microen vironment (SCID_FL mice). In these T cells, the TCR Vβ repertoire is broad, N(D)N regions are significantly longer, and contain regular rates of template-independent N nucleotides. In striking contrast, a Vβ8.2 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 microen vironment 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 Vβ 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.