Spontaneous mutation at position 114 in H-2Kd affects cytotoxic T cell responses to influenza virus infection

Abstract

Vaccinia virus (VV)-encoded MHC class I K(d) molecules which differ by a single amino acid change from glutamine (K(dw), wild type) to histidine (K(dm), mutant) at position 114 located in the floor of the peptide binding groove were compared in terms of peptide binding and cytotoxic T (Tc) cell recognition. Most anti-viral Tc cells were nor affected or only marginally affected. However, the K(dm) molecule did not detectably present the immunodominant peptide (NPP147-155) of influenza virus nucleoprotein (NP), encoded by the full-length NP gene either in influenza A virus or recombinant W. This defect could be overcome by using exogenous synthetic NPP147-155 or translation from a minigene encoding NPP147-155 in W. K(dw) presented NPP147-155 encoded by the full-length NP) gene, but K(dw)-NPP147-155 complexes were at least 100-fold less abundant than after translation from a minigene. Show more