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 (TC R) using V beta 8.2 gene elements, together with short N(D)N regions. Here we analyzed MBP-specific TCR from Lewis T cells differentiating i n chimeric thymuses of Lewis rat/SCID mouse chimeras, in the absence o f an intact rat thymic microenvironment (SCIDFL mice). In these T cell s, the TCR V beta repertoire is broad, N(D)N regions are significantly longer, and contain regular rates of template-independent N nucleotid es. In striking contrast, a V beta 8.2 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 (SCIDFL/FT mice). A T cell repertoire resembling the one in SCIDFL mice is used by T cells of intact Lewis rats following immunization with a truncate d epitope of MBP, p69-86. Also this selection generates a broad TCR V beta pattern with long N(D)N regions, and higher numbers of N nucleoti des. These results show that both intrathymic repertoire selection, an d extrathymic peptide priming exert profound effects on the TCR usage in the anti-MBP response of Lewis rats.