Mls and the helper T-cell repertoire: II. Does the Mls gene product influence the formation of the T-cell repertoire? Studies with Mls tolerance.
In the formation of a repertoire, T cells are selected through a window of autoreactivity which is defined by a low boundary representing the minimal autoreactivity required to enter the T-cell compartment and a high boundary which determines the highest admissible autoreactivity. We propose that the Mls gene product down regulates autoreactivity and thus modifies the formation of the T-cell repertoire. Given the polymorphism of Mls and the assumption that Mlsb is more inhibitory than Mlsd, it is conceivable that Mlsb (responder) mice admit into their T-cell compartment T cells with higher autoreactivity than Mlsd mice. We suggest that it is this highly autoreactive fraction of Mlsb T cells which responds in the overt Mls response. We show that Mls tolerance eliminates T cells responding in the overt Mls response but not T cells responding in the latent Mls response. This is consistent with the finding that T cells responding in the latent Mls response occur in Mlsb as well as in Mlsd mice.