The specific binding of peptide ligand to Ld class I major histocompatibility complex molecules determines their antigenic structure.
To better understand the biological implications of the association of ligand with major histocompatibility complex class I molecules, we have studied the Ld molecule of the mouse. The culturing of various nonselected cell lines with three different known Ld peptide ligands resulted in a two- to fourfold specific increase in surface Ld expression as detected by 10 of 11 different monoclonal antibodies (mAbs) recognizing Ld epitopes. These findings suggest that Ld molecules are not saturated with endogenous peptide ligands and thus have accessible binding sites. Exploiting this feature of Ld we demonstrate that the physical association of Ld with ligand is exquisitely specific, indicating that they function in determinant selection. In addition, a non-peptide-bound antigenic variant of Ld was specifically detected with an exceptional mAb designated 64-3-7. In comparison with other Ld molecules, 64-3-7+ Ld molecules are not peptide ligand inducible, are more susceptible to proteolysis, lack beta 2 microglobulin association, and display a slower rate of oligosaccharide maturation. In spite of their deficiencies, the non-ligand-associated 64-3-7 Ld molecules were detected on the surface of all cell types tested; however, they appear not to be recognized by alloreactive cytotoxic T lymphocytes.
Department of Genetics, Washington University School of Medicine, St. Louis, Missouri 63110.
W R
WR
Lie
N B
NB
Myers
J M
JM
Connolly
J
J
Gorka
D R
DR
Lee
T H
TH
Hansen
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal; D000954:Antigens, Surface / Q000378:metabolism; D001692:Biological Transport; D002460:Cell Line; D002478:Cells, Cultured; D000939:Epitopes / Q000276:immunology*; D005434:Flow Cytometry; D006183:H-2 Antigens / Q000276:immunology / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000276:immunology / Q000378:metabolism*; D008024:Ligands; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000138:chemical synthesis / Q000378:metabolism*; D011233:Precipitin Tests; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D000939:Epitopes; D006183:H-2 Antigens; D015395:Histocompatibility Antigens Class I; D008024:Ligands; D009842:Oligopeptides