We previously described a somatic cell expressing a variant H-2Dd molecule that did not serve as a target for alloreactive anti-Dd CTL. The mutant cell line had been isolated by its failure to express a serological epitope present on the H-2Dd alpha 3 domain. In the present study the alpha 3 domain of the Dd molecule of this somatic cell variant was sequenced and a single nucleotide change resulting in a glutamic acid to lysine substitution at residue 227 was identified. This change was reproduced in the cloned H-2Dd gene by oligonucleotide-directed mutagenesis. Cells transfected with this mutant gene were not killed by anti-H-2Dd CTL. Because previous studies using hybrid H-2 class I molecules had established that the alpha 3 domain does not express allele-specific determinants recognized by CTL, our results raise the possibility that residues in the alpha 3 domain of H-2 class I molecules are critical for CTL recognition and constitute a conserved (or monomorphic) determinant recognized by CTL.
A single amino acid substitution in the alpha 3 domain of an H-2 class I molecule abrogates reactivity with CTL.
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T A Potter, J A Bluestone, T V Rajan; A single amino acid substitution in the alpha 3 domain of an H-2 class I molecule abrogates reactivity with CTL.. J Exp Med 1 October 1987; 166 (4): 956–966. doi: https://doi.org/10.1084/jem.166.4.956
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