Recognition of a single amino acid change on the surface of a major transplantation antigen is in the context of self peptide.
The transcripts encoding two strongly alloantigenic class I mutant molecules, Kdm4 and Kdm5, were characterized and found to encode products that differ from the parental Kd glycoprotein by single amino acid substitutions. The Kdm4 molecule has an amino acid change at position 114, an integral component of a beta-sheet associated with pockets D and E of the peptide binding site. The basis for strong alloantigenicity of the variant molecule can be attributed to differences in peptide binding that were visualized by HPLC analysis of eluted peptides. In contrast, the Kdm5 molecule differs from the parent at position 158, a component of the alpha-helix that is not associated with any of the pockets of the peptide binding site. No differences in peptide binding by Kdm5 in comparison with the parent Kd molecule were seen by HPLC, suggesting that the variant and parent molecules bind the same set of peptides. The ability of (dm4 x dm5) F1 hybrid mice to recognize and lyse BALB/c stimulator cells indicates that the alloantigenic properties determined by the 158 substitution result from the interactions of the alpha-helix regions (changed in dm5) with the pockets of the binding site (changed in dm4). We conclude that self peptides shared by the F1 hybrid and the BALB/c stimulator cells are recognized in the context of structural features of the helices of the Ag-presenting molecule as alloantigenic determinants.
Pullen
J K
JK
Department of Immunology, Mayo Foundation for Education and Research, Rochester, MN 55905.
Tallquist
M D
MD
Melvold
R W
RW
Pease
L R
LR
D000595:Amino Acid Sequence; D000818:Animals; D001324:Autoantigens / Q000276:immunology; D001483:Base Sequence; D001665:Binding Sites; D005260:Female; D006183:H-2 Antigens / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009154:Mutation; D010455:Peptides / Q000276:immunology; D012326:RNA Splicing
D001324:Autoantigens; D006183:H-2 Antigens; D010455:Peptides