Use of H-2 mutations to quantitate alloreactivity: Alloreactivity is strongest against H-2 antigens which are closest to self

Lymph-node cells from H-2 allogeneic, intra-H-2 recombinant and H-2 mutant congenic strains were sensitized in limiting dilution cultures to quantitate the cytotoxic T-lymphocyte precursor frequencies (CTL.Pf) against antigens encoded by different regions of the H-2 complex. When four H-2K^b mutants of C57BL/6 (B6) were tested, we observed anti-B6 CTL.Pf that were as high or higher than those of recombinant strains which differ from B6 at the K end of the H-2 complex. Relative to strains completely H-2 allogeneic to B6, the CTL.Pf in H-2^bm1, H-2^bm3 and H-2^bm5 averaged 40-50 percent, and H-2^bm8 averaged 140 percent. Recombinant strains B10.A (4R) and B10.D2 (R103), which differ from B6 at the K end of the H-2 complex, averaged 60 percent of the completely H-2 allogeneic value. Since the mutant and wild-type gene products have no serological and minimal structural differences relative to other alleles at H-2K, these results indicate that the CTL.Pf does not increase with increasing H-2 antigenic disparity between any two strains. Rather, the data suggests that the T-cell receptor repertoire recognizes those H-2 molecules or determinants closest to self.