Spontaneous mutation at position 114 in H-2Kd affects cytotoxic T cell responses to influenza virus infection.
Vaccinia virus (VV)-encoded MHC class I Kd molecules which differ by a single amino acid change from glutamine (Kdw, wild type) to histidine (Kdm, 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 not affected or only marginally affected. However, the Kdm 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 VV. This defect could be overcome by using exogenous synthetic NPP147-155 or translation from a minigene encoding NPP147-155 in VV. Kdw presented NPP147-155 encoded by the full-length NP gene, but Kdw-NPP147-155 complexes were at least 100-fold less abundant than after translation from a minigene.
Müllbacher
A
A
Division of Immunology and Cell Biology, John Curtin School of Medical Research, Australian National University, Canberra City, ACT. arno.mullbacher@anu.edu.au
Lobigs
M
M
Yewdell
J W
JW
Bennink
J R
JR
Tha Hla
R
R
Blanden
R V
RV
D000818:Animals; D006183:H-2 Antigens / Q000737:chemistry / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D009154:Mutation; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins; D009976:Orthomyxoviridae Infections / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology; D013329:Structure-Activity Relationship; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014758:Viral Core Proteins / Q000276:immunology
D006183:H-2 Antigens; C024755:H-2K(K) antigen; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins; D010446:Peptide Fragments; D014758:Viral Core Proteins