T-CELLS FROM UNPRIMED MICE RESPOND TO THE SELF ANTIGEN HEME, IN A CLASS-II RESTRICTED MANNER, AT A FREQUENCY SIMILAR TO ALLORESPONSES

Heme is a non-protein autoantigen which stimulates potent proliferativ e responses by T cells from unprimed mice of some strains, These studi es show that T cells responding to heme in primary responses are predo minantly CD4(+), classically I-A restricted, and use diverse TCR chara cterized by the expression of distinct V, D and J gene segments, These characteristics distinguish heme from superantigens and mitogens whic h exhibit degenerate MHC restriction and, in the case of superantigens , restricted V gene usage, Using limiting dilution analysis these stud ies also show that the potent primary response of H-2(s) mice reflects a high frequency (0.26-0.45%) of heme responsive T cells in the perip hery, comparable to the frequency of alloresponsive T cells reported b y others in primary mixed lymphocyte reactions, In contrast, heme resp onsive T cells occur at similar to 10-fold lower frequency in unprimed H-2(d) mice (0.03%). To determine the antigen recognized by heme reac tive T cells, the mass spectra of peptides eluted from the high respon der haplotype, I-A(s), were examined, These indicated a markedly diffe rent molecular weight distribution of peptides isolated from cells gro wn in the presence of heme, compared with those from cells grown in it s absence. This suggests that heme mediates the expansion of diverse T cells in the peripheral repertoire by a mechanism similar to that for allogeneic responses in which the profile of naturally processed pept ides bound to the MHC class II molecule is changed.