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

Abstract

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.

New tools to trace populations of inflammatory cells in the CNS

“…In this experiment, it was essential to learn whether the developing TK‐tsA transgenic T‐cells matured within the endogenous SCID mouse, or within the grafted wild‐type rat thymus. Using the TK‐tsA cassette as marker for the developing rat T‐cells, the migration of these lymphocytes to and their maturation within the grafted rat thymus could be unequivocally demonstrated (Kääb et al, 1996, 1998; Wekerle et al, 1996).…”