T lymphocytes responding to Mls-locus antigens are Lyt-1+, 2- and I-A restricted.

We have investigated primary and secondary responses of mouse splenic T cells to strong mixed lymphocyte stimulating antigens controlled by the Mls locus using MHC-identical mixtures of cells. Our studies show that strong primary Mls-locus specific responses involve recognition of self I-A antigens, since BUdR and light suicide or F1 into parent radiation bone-marrow chimeras both demonstrate a preference of unprimed F1 T cells to respond to Mls-locus antigens associated with one parent's MHC antigens. Furthermore, conventional anti-I-A antisera and monoclonal anti-I-A antibody both inhibit Mls-locus responses in an MHC-specific manner. Finally, as is typical of T cells responding to I-A antigens or to nominal antigens associated with self I-A, Mls-locus responses are mediated by Lyt-1+, 2 cells. One striking finding in these studies was the very high frequency of cells capable of responding to Mls-locus antigens, the highest being 1/300 splenic T cells. This plus evidence for recruitment during primary Mls-locus responses may account for reports of a lack of I-A restriction in secondary anti-Mls locus responses to strong Mls-locus antigens, a finding with which we concur. The possibility that these secondary responses between noncongenic strains of mice may be directed at other genetic loci is also discussed. These experiments leave open the question of the biological role of the Mls-locus and of the very large number of T cells reactive to it.